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April 2007 Vol. LXXXV, No. 8

MonthlyMeetingEsselen Award Meeting at Harvard,Prof. Michael Marletta, UCALBerkeley, speaks on “Nitric Oxide in Biology: From Discovery toTherapeutics”

SummerResearchScholar“Engineering Monovalent Avidin” by Jessica A. Lynch, Mark Howarthand Alice Y. Ting

Book Review“Nontraditional Careers forChemists: New Formulas inChemistry,” reviewed by Lynne A.O'Connell

Symposium“Advances in Chemical Sciences” tobe held March 30, 2007 at the RoyalSonesta Hotel in Cambridge, MA

2 The Nucleus April 2007

IntroductionThe binding of the vitamin biotin by avidin or streptavidin isone of the tightest interactions known in nature. These twoproteins are widely used by biologists for biomolecule label-ing, immobilization and purification. Streptavidin andavidin have also shown promise in medical applications, forexample, delivering radioisotopes to tumors.

Despite the existence of numerous applications forstreptavidin and avidin, many limitations still exist.Because both proteins are tetramers, they can tetramerizethe biotin conjugates to which they bind. This can lead toaggregation, interfering with the use of avidin/streptavidinfor tracking cell surface proteins and promoting comple-ment activation when used in vivo. Also, immunogenicity isa problem, particularly with streptavidin. As the therapy isrepeated, antibodies are generated against the foreign pro -tein and efficacy decreases. Another challenge is to engi-neer the avidin/streptavidin to bind biotin analogs that arenot present endogenously in the body, to give an orthogonallabeling system. The Ting lab is working to address all ofthese limitations, by rational engineering and selection ofrandom mutants.

The lab recently solved the valency problem by devel -oping a monovalent streptavidin with a single femtomolarbiotin binding site, which was utilized in cross-linking-freelabeling of biotinylated neuroligin-1 on the surface of livingneurons. It is essential to keep streptavidin tetrameric orbiotin binding affinity decreases ten thousand fold. Thegoal was to produce a streptavidin tetramer consisting ofthree subunits unable to bind biotin (termed “Dead”) andone subunit that binds biotin as effectively as wild-typestreptavidin (termed “Alive”). To generate the desiredmutants, three alterations were made in the binding site. A6His tag was then added to the Alive subunit and then com-bined with Dead and Alive subunits at a 3:1 molar ratio inthe presence of guanidinium hydrochloride. The subunitswere then rapidly refolded and monovalent streptavidin wasthen purified on a nickel-nitrilotriacetic acid column1.

The Ting lab has also developed a method of si te-spe-cific labeling of cell surface proteins utilizing biotin ligase.E. coli biotin ligase (BirA) sequence-specifically ligatesbiotin to a 15-amino-acid acceptor peptide (AP) 2. Cell sur-face proteins are then labeled by detecting the biotin withmonovalent streptavidin.

The goal of my project was to engineer a monovalentavidin, for use in drug targeting and cellular labeling. Thisis important because avidin behaves differently from strep-tavidin in vivo; notably, it is much less immunogenic than itsbacterial analog.

ResultsThe first task was to determine an appropriate expres -

sion and purification method for avidin, which, whenexpressed cytoplasmically, forms inclusion bodies which aretime-consuming to purify. We decided to express the avidinperiplasmically, and the avidin was thus engineered to havea bacterial leader sequence directing the protein to theperiplasmic space. Because the yield was low and theleader was not cleaved properly, we decided on severalmethods of improvement, including using 3-fold less IPTG(70 µM), and expressing the protein under stress conditions:0.5M Sorbitol, 4% NaCl and 10mM glycine betaine 3 (Fig.1). We also experimented with GET buffer4 (0.5M glucose,1mM EDTA and 200 mM Tris, pH 7.4) with 0.15 mg/mLlysozyme and sonication at 40% duty cycle 30 seconds on,30 seconds off, two times to decrease the viscosity of thelysate and increase our yield. To aid with leader cleavage,we added a 4-amino acid spacer to the N-terminus of theprotein. Despite these improvements, subsequent yields of fof the Ni-NTA column remained low (Fig. 2).

SUMMER RESEARCH SCHOLAR Engineering Monovalent AvidinJessica A. Lynch, Mark Howarth, Alice Y. TingDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge MA, 02139

continued on page 10

Figure 1

Figure 2

The Nucleus is distributed to the members of the Northeastern Section of the American Chemical Society, to the secretaries of the Local Sections, and to editors of all local A.C.S. Section publications.Forms close for advertising on the 1st of the month of the preceding issue. Text must be received by theeditor six weeks before the date of issue.Editor: Michael P. Filosa, Ph.D., editor, ZINK Imaging LLC, 1265 Main Street,

Waltham, MA 02451 Email: Michael.Filosa(at)zink.com; Tel: 781-386-8479.Associate Editors: Myron S. Simon, 20 Somerset Rd., W. Newton, MA 02465, Tel: 617-332-5273

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Board of Publications: Vivian K. Walworth (Chair), Mary Mahaney, David Cunningham Business Manager: Karen Piper, 19 Mill Rd., Harvard, MA 01451, Tel: 978-456-8622Advertising Manager: Vincent J. Gale, P.O. Box 1150, Marshfield, MA 02050,

Tel: 781-837-0424; FAX: 781-837-1453Contributing Editors: Morton Hoffman, Feature Editor; Dennis Sardella, Book Reviews Calendar Coordinator: Sheila Rodman, email: srodman(at)konarka.comPhotographers: Morton Z. Hoffman and James PhillipsProofreaders: Donald O. Rickter, Myron S. Simon, Vivian K. Walworth, E. Joseph BilloWebpage: Webmaster: Sathish Rangarajan, sathish.rangan2(at)gmail.comCopyright 2007, Northeastern Section of the American Chemical Society, Inc.

The Nucleus April 2007 3

The Northeastern Section of the AmericanChemical Society, Inc.Office: Marilou Cashman, 23 Cottage St., Natick, MA 01360. 1-800-872-2054 (Voice or FAX) or 508-653-6329. e-mail: mcash0953(at)aol.comAny Section business may be conducted via the business office above.NESACS Homepage:http://www.NESACS.orgSathish Rangarajan, WebmasterACS Hotline, Washington, D.C.: 1-800-227-5558Officers 2007Chair:Mukund Chorghade14 Carlson Circle, Natick, MA 01360508-651-7809 and 308-3891Chorghade(at)comcast.netChair-Elect:Marietta SwartzChemistry Department, Umass-BostonBoston, MA 02125617-287-6146; marietta.swartz(at)umb.eduImmediate Past Chair:Patricia MabroukChemistry Department, Northeastern UniversityBoston, MA 02115613-373-2845; p.mabrouk(at)neu.eduSecretary:Michael SingerSigma-Aldrich3 Strathmore Rd., Natick, MA 01360508-651-8151X291; msinger(at)sial.comTreasurer:James Piper19 Mill Rd., Harvard, MA 01451978-456-3155, piper28(at)attglobal.netAuditor:Anthony RosnerArchivist:Myron S. Simon20 Somerset Rd.Newton, MA 02465; 617-332-5273Romysimon(at)mindspring.comTrustees:Joseph A. Lima, Esther A. H. Hopkins,Michael E. StremCouncilors Alternate CouncilorsTerm Ends 12/31/2007Thomas R. Gilbert Arlene W. LightMichael J. Hearn Timothy B. FrigoMichael Singer Mary MahaneyPamela Nagafuji Mark FroimowitzTerm Ends 12/31/2008Doris I. Lewis Patrick M. GordonMorton Z. Hoffman Michael P. FilosaChristine Jaworek-Lopes Lawrence ScottMary Burgess Liming ShaoDonald O. Rickter S.B. RajurTerm Ends 12/31/2009Catherine Costello Julia H.MiwaPatricia Mabrouk Alfred ViolaMichaeline F. Chen Jerry P. JasinskiDorothy J. Phillips Eva B. BinnunAmy Tapper Barney Grubbs

All Chairs of standingCommittees, the editor of THE NUCLEUS, and the Trustees of SectionFunds are members of theBoard of Directors. AnyCouncilor of the American Chemical Societyresiding within the section area is an ex officiomember of the Board of Directors.

ContentsSummer Research Scholar _______________________________2“Engineering Monovalent Avidin” by Jessica A. Lynch, Mark Howarth and Alice Y. Ting

Announcements________________________________________4Northeast Student Chemistry Research Conference 2007, Call for Volunteersfor the Boston National ACS Meeting, Boston Regional Inorganic Meeting

Monthly Meeting _______________________________________5Esselen Award Meeting, Prof. Michael A. Marletta to speak on “Nitric OxideIn Biology: From Discovery to Therapeutics”

Book Review __________________________________________6“Nontraditional Careers for Chemists: New Formulas in Chemistry,” Reviewed By Lynne A. O'Connell, Department of Chemistry, Boston College

Announcements________________________________________7Advances in Chemical Sciences Symposium, Summerthing 2007

Historical Notes _______________________________________8Daniel F. Lord and Kenneth A. Moon

Announcement ________________________________________9A viewing and discussion of “Forgotten Genius” at Bridgewater State College

Announcement _______________________________________114th Annual NESACS Golf Tournament

The Gustavus J. Esselen Award __________________________12NESACS Candidates for Election 2007 ____________________12Cover: April Speaker, Professor Michael A. Marletta,

(Photo Courtesy of Prof. Marletta)

Deadlines: Summer 2007 Issue: June 15, 2007September 2007 Issue: July 13, 2007

Call forVolunteersBoston National ACS MeetingThe National ACS meeting will beheld in Boston from August 19-23,2007. The Northeastern Section willhost the meeting. The Hospitality Cen-ter, General Interest Program and Stu-dent Personnel along with volunteerworkers are being organized for themeeting. The Hospitality Center willneed volunteers to provide informationon points of interest, transportation,restaurants, etc. The center will beopen from approximately 9AM to 5PMdaily. Hours for volunteers are flexible.More information on the schedulingwill be forthcoming. For more infor-mation, please contact the following:Hospitality—Mary Burgess617-522-9165 mbrburgess(at)aol.comGeneral Chairperson-(Planning Committee) - Robert LichterRlichter(at)MerrimakLLC.com ◆◆


Corporate Patrons and Golf IridiumAstra Zeneca R&D BostonGenzyme Drug Discovery & DevHovioneIBMIRIX PharmaceuticalsJohnson-Matthey Pharma SolutionsLyophilization Service of New EnglandMerckPhasex CorporationSepracorStrem Chemicals, Inc.Zone EnterprisesCorporate Sponsors and GolfRhodiumAerodyne Research, Inc.Cambridge Isotope LaboratoriesCambridge Major LaboratoriesNew England BioLabs, Inc.PfizerSigma-RBIShasun Pharma SolutionsDonors and Golf TungstenConsulting Resources Corp.Dishman Pharmaceuticals

and Chemicals LimitedHoughton Chemical CompanyOrganix, Inc.Vertex

Northeast Student ChemistryResearch Conference 2007The 9th Annual Conference is open toundergraduates, graduates, and postdoctoral fellows in all areas ofchemical research.

Saturday, April 21, 2007MITThe Ray and Maria Stata Center9 am - 4 pmVisit the NESACS YCC for moreinformation: http://www.nsycc.org/Abstracts will be accepted on thissite. There is no registration fee.Students are invited to present a posteror a 15-minute oral presentation.

Deadlines:Oral presentation: April 6, 2007Poster presentations: April 13, 2007 ◆◆

Call forPapers

BRICMeetingBoston Regional InorganicChemistry Meeting (BRIC) tobe held at UNHThe 13th Boston Regional InorganicChemistry (BRIC) Meeting, is sched-uled for Saturday, May 5, 2007, at theUniversity of New Hampshire inDurham, NH from 9:30 am to 3:30 pm.The program will include three to fourlecturers and presentation of posters.Speakers will include Rachel N.Austin, Bates College; Howard H. Pat-terson, University of Maine at Orono;and Dean E. Wilcox, Dartmouth Col-lege.Informal lunch will be provided.Questions contact Roy Planalp,roy.planalp(at)unh.edu. ◆◆

BiographyMichael A. Marletta was born inRochester New York on February 12,1951. After an A.B. degree in biologyand chemistry from SUNY College atFredonia, in 1973, he received a Ph.D.in 1978 from the University of Califor-nia, San Francisco, working under Prof.George L. Kenyon. He then joinedProf. Christopher Walsh at M.I.T. for a2-year postdoctoral appointment.

Marletta then joined the faculty atM.I.T. as an Assistant Professor of Tox-icology in the Department of Applied

AbstractNitric Oxide in Biology: FromDiscovery to Therapeutics Nitric oxide (NO) is now firmly estab-lished as a vital mediator in mam-malian biochemistry. Parallel lines ofresearch focused on mechanisms ofimmune system killing and cardiovas-cular function converged in the middle1980’s on NO as the common compo-nent. NO is highly toxic, consistentwith a killing function in the immunesystem but inconsistent with a role inthe cell-to-cell signaling. The subse-quent discovery of nitric oxide syn-thase revealed a complex redox proteinthat carries out the conversion of L-arginine to NO and citrulline. Impor-tant mechanistic questions still remain;however, much progress has beenmade on this complicated reaction.Given the toxicity of NO, signalingmechanisms must respond to low con-centrations. The primary NO receptoris guanylate cyclase, an enzyme thatconverts GTP to cyclicGMP once acti-vated by NO. Biological responsessuch as vasodilation are mediated bycyclicGMP. The mechanism of guany-late cyclase activation by NO has beenextensively studied and moleculardetails continue to emerge. The funda-mental studies on nitric oxide synthase,guanylate cyclase and other enzymesin NO pathway have found applicationin a number of diseases such as septicshock and erectile dysfunction. ◆◆


Continued on page 8

Monthly MeetingThe 878th Meeting of the Northeastern Section of the AmericanChemical SocietyEsselen Award MeetingThursday, April 12, 2007Harvard University, Cambridge, MAHarvard Faculty Club, 20 Quincy Street

2:30 pm Career Services Presentations and Resume Reviews, MukundChorghade, Chair NESACS; Megan Driscoll and Jennifer Sass ofPharmaLogics Recruiting.

5:30 pm Social Hour,

6:30 pm Dinner

8:15 pm Award Meeting, Mallinckrodt Building, 12 Oxford StreetPfizer Lecture Hall (MB23), Ground FloorDr. Mukund Chorghade, NESACS Chair, presidingWelcome - Dr. Robert Langer, Chair, Esselen Award CommitteeThe Esselen Award – Dr. Myron Simon, Founding Member of the

Esselen Award CommitteeIntroduction of the Award Recipient – Dr. Robert Langer,

Massachusetts Institute of TechnologyPresentation of the Award – Gustavus J. Esselen, IIINitric Oxide in Biology: From Discovery to Therapeutics.

Dr. Michael A. Marletta, Aldo DeBenedictus Distinguished Pro-fessor of Chemistry and Chair of the Department of Chemistry,University of California, Berkeley

Dinner reservations should be made no later than noon, Friday, April 6.Please call or fax Marilou Cashman at (800) 872-2054 or e-mail atMCash0953(at)aol.com. Reservations not cancelled at least 24 hours inadvance must be paid. Members, $30.00; Non-members, $35; Retirees, $20;Students, $10.THE PUBLIC IS INVITEDAny one who needs special services or transportation, please call MarilouCashman a few days in advance so that suitable arrangements can be made.Free Parking in the Broadway Street Garage (3 rd level or higher), enter fromCambridge Street via Felton Street. Directions to the Harvard Faculty Clubcan be found at http://www.hfc.harvard.edu/ .Next Meeting: The May meeting is Education Night. It will be on May 10,2007 at Northeastern University (Raytheon Amphitheater). Speaker TBA.Please note that the board meeting will begin a half hour early (4pm to ensurethat it is over in time for the reception, etc. (The reception will be at 5:15pm anddinner will be at 6pm.)

Chemists are passionate about research.Investigating the unknown, askingquestions about chemical reactions andprocesses, designing and performingexperiments to solve problems—theseare the activities that get a chemist’screative juices flowing. But for somechemists, a moment arrives when theyrealize their passion for laboratoryresearch is no longer there; at thispoint, the question inevitably arises,“What do I do with my chemistrydegree now?” The book Non-Tradi-tional Careers for Chemists: New For-mulas in Chemistr y, by Lisa M.Balbes, provides a comprehensiveanswer to this question.

The title of each chapter in thebook begins with the words “Chem-istry and … .” A sampling of the sub-

jects that replace the ellipsis shows thevariety of fields that are described:communication, information science,sales and marketing, business develop-ment, regulatory affairs, public policy,computers, and education. The begin-ning of each chapter introduces thereader to the profession and lists thevarious positions that would be appro -priate for someone in this field with abackground in chemistry . Forinstance, the chapter entitled “Chem-istry and Patents” describes the jobs ofpatent examiner, patent searcher, tech-nical specialist and patent agent, inaddition to patent attorney. Profiles ofactual people who hold these positionsfollow the job descriptions. These pro-files are the heart of the book and givethe reader real insights into the profes -

sions that are discussed. Each person who is profiled starts

by describing the position that he orshe currently holds, including detailsof daily tasks and an overview of allthe responsibilities encompassed bythe job. Some indication is usuallygiven concerning the amount of travelrequired for the position, as well as thesalary, which is simply compared tothat of a chemist working at the benchin an industrial setting. In the lengthi -est section of each profile, the individ -ual explains how he or she arrived atthe current position. These sectionshelp the reader to see what factorsprompt people to leave the laboratorysetting, what advanced degree optionsshould be considered if one is going toenter the line of work described, andwhat personality traits are importantfor success in the field. Since many ofthe speakers have been employed in avariety of environments, the advan-tages and disadvantages of working insmall versus large companies are dis-cussed, as are the pros and cons ofowning one’s own business. In an“Advice” section, the speaker is askedto provide specific suggestions on howto enter and succeed in the profession.The profiles conclude with predictionsabout the future direction of the field,as well as a list of references where thereader can find more information.

There are a number of themes thatrecur throughout the book. Virtuallyeveryone who is profiled indicates that,although they are no longer working ina laboratory, the experience theygained while studying chemistry pre-pared them well for their currentcareer. The skills learned in lectureand lab courses that are repeatedlycited as being invaluable include theability to break down complex issues

Book ReviewNontraditional Careers for Chemists: New Formulas in Chemistry, by Lisa M. Balbes (Oxford University Press, 2006, 320 pp., ISBN 0195183673; $27.95 paperback)Reviewed by Lynne A. O’Connell Department of Chemistry, Merkert Chemistry Center Boston College, Chestnut Hill, MA 02467

Continued on page 7


into simpler parts in order to solveproblems, as well as the ability toacquire data, analyze it and assess itsaccuracy. In addition, having a strongbackground in science facilitates com-munication with practicing scientists,which is a necessary part of all the pro-fessions covered. The excitement asso-ciated with talking to scientists whoare working on cutting edge researchwas mentioned by many as being ahighly rewarding aspect of their job.Some generalizations can also bedrawn from the advice given by thoseprofiled—an ability to adapt to newsituations is essential; one must alwaysbe ready to take advantage of newopportunities; and networking at con-ferences and through professional soci-eties is important for advancement.

While not explicitly stated, itappears that the book is intended forstudents at both the graduate andundergraduate levels. However, thereare few profiles of people who are justembarking on their careers. Most haveadvanced degrees or have been in theirfields a long time and risen to a high-level positions. While the absence ofrecent chemistry graduates might ini-tially appear to be an oversight, itbecomes clear that the experiences ofthese more seasoned individuals havegiven them big picture views of theirrespective fields, which allows them tospeak about opportunities at everylevel, from entry to executive. Theirknowledge of and enthusiasm for theirfields is inspiring. In fact, the vastarray of opportunities presented was soenticing that it made me want to goback and major in chemistry all overagain. ◆◆

Book ReviewContinued from page 6


We wish to announce that the inaugu-ral “Advances in Chemical SciencesSymposium” conference in the Bostonarea will be held on March 30, 2007;the symposium will begin at 9.00 a.m.The venue will be the Royal SonestaHotel in Cambridge, MA. Under theauspices of these conferences, eminentscientists from the strategic triad ofgovernment and industry and academiawill deliver plenary lectures. The con-ference will bring together 200+ scien -tists for a scholarly event focusing onmedicinal chemistry, organic synthesisand methodology. Robert Grubbs (Cal-tech), William Greenlee (ScheringPlough), Eric Jacobsen (Harvard) andSteven Ley (Cambridge). The pro-posed topical focus areas – medicinalchemistry, pharmaceutical and organicsynthesis – are areas where the chemi -cal enterprise in our area has a well-

deserved reputation for excellence. Weinvite all of you to join us for thisevent, share ideas, and build networks.The symposium registration fee will be$35.00. Please send your contact infor -mation and checks payable toNESACS to Dr. James Piper, TreasurerNESACS, 19 Mill Road, Harvard, MA01451Please contact the following for addi-tional details:

Chorghade(at)comcast.net,

Michael.P.Pollastri(at)pfizer.com,

Leslie.Mcquire(at)novartis.com,

ralphscannell(at)comcast.net,

jamedio(at)ziopharm.com ◆◆

SymposiumInaugural Symposium: Advances In Chemical Sciences Symposium sponsored by NESACS, IUPAC and RSC-US

Join your NESACS friends and theirfamilies as we travel to LaLecheurPark in Lowell, MA to watch the Low-ell Spinners (BOS) take on the AuburnDoubledays (TOR) in a Class A base-ball game. The game will be on Sat-urday July 14th, 2007 at 5:00 PM.

Following the game, stick aroundto play catch on the field and watch afeature presentation on the state of theart video board. Tickets are limitedand will be available on a first come,first ticketed basis. Cost will be$10.00 per ticket.

For directions to LaLecheur Park,see the Lowell Spinners Website atwww.Lowellspinners.com.

For reservations, please call MarilouCashman at the NESACS office at 1-800-872-2054 or (508) 653-6329 ore-mail to mcash0953(at)aol.com. ◆◆

Summerthing 2007 Lowell Spinners Baseball Saturday, July 14, 2007 5:00 pm

Some Pregame Festivities at LaLecheur Field in2005: Peter Filosa prepares to throw a ceremo-nial first pitch. Rene Rancourt of Boston Bruinsfame followed with his famous rendition of theNational Anthem and O Canada.

(Photo by Michael Filosa)


Biological Sciences. He was promotedto Associate Professor in 1986. In 1987he joined the faculty at the Universityof Michigan as Associate Professor ofMedicinal Chemistry in the College ofPharmacy and, in 1989, Associate Pro-fessor of Biological Chemistry in theMedical School. In 1991 he was pro-moted to Professor in both departmentsand appointed the John G. Searle Pro-fessor of Medicinal Chemistry. In 1997he became an Investigator in theHoward Hughes Medical Institute.Marletta moved to the University ofCalifornia, Berkeley in 2001, where heassumed the positions of Professor ofChemistry, Department of Chemistry,and Professor of Biochemistry andMolecular Biology, Department ofMolecular and Cell Biology. He alsoholds an appointment as Professor ofCellular and Molecular Pharmacologyat UCSF and Faculty Scientist at theLawrence Berkeley National Lab. Hewas appointed the Aldo DeBenedictisDistinguished Professor of Chemistryin 2002. On 1 July 2005, he becameChair of the Department of Chemistryat Berkeley.

Awards he has received includethe George H. Hitchings Award forInnovative Methods in Drug Discoveryand Design (1991) sponsored by theBurroughs Wellcome Fund and a Fac-ulty Recognition Award from the Uni-versity of Michigan (1992). He wasawarded the Outstanding AlumniAchievement Award from SUNY Fre-donia in 1993. In 1995 he received aMacArthur Fellowship awarded by theJohn D. and Catherine T. MacArthurFoundation. He was elected SeniorFellow in the Michigan Society of Fel -lows and elected to the SUNY HonorRole in 1996. He was elected to theInstitute of Medicine in 1999. He wasawarded the Distinguished FacultyLectureship Award in BiomedicalResearch by the University of Michi-gan Medical School for 2000 and hon-ored as the Michigan Scientist of theYear (2000) by the Impression 5 Sci-ence Museum. Also in 2000, he was a

BiographyContinued from page 5

Daniel F. LordDaniel F. Lord died May 25, 2006 inMarblehead, MA. He was 82. He wasborn in Cambridge, MA in 1923, grad-uated from Marblehead High School in1941, and began college at MIT. Heserved in the U.S. Army in World WarII, then returned to MIT, graduatingwith the Class of 1947. Subsequently,he studied chemical engineering atLehigh University.

Lord worked as a chemical engi-neer at J.S.Barnet and Sons in Lynn, atGillette in North Andover, and otherfirms. He also ran the Cliff FamilyTree Farm in Salem, NH. He was amember of the American ChemicalSociety, the American Institute ofChemical Engineers and MENSA.

He is survived by his wife of 56years, Norma MacMullen Lord, adaughter, Karen Cunningham, twosons, Jonathan K. Lord and Alan Lord,a brother, Robert S. Lord, six grand-children, and one great-grandchild.

Kenneth A. MoonKenneth A. Moon, a long time mem-ber of the American Chemical Society,died on March 16, 2006. He held B.S.and M.S. degrees from Queens Univer-sity in Kingston, Ontario and a Ph.D.in Physical Chemistry from M.I.T. Hischemical career was at the Army labo-ratories at the Watertown Arsenal.

He was the recipient of manyawards and honors for his dedication toconservation and environmental issues.He was a founding member of the Sud-bury Valley Trustees and the WaylandConservation Commission. He is sur -vived by his wife,Elizabeth. sonsDavid and Peter, daughters-in-lawKrista and Kate and four grandchildren.

MSSWe present here short biographies ofchemists and chemical engineers whosedeaths have been reported to us duringthe past year. We thank members of theNortheastern Section who have sent usobituary notices appearing in newspa-pers we do not see. ◆◆

Historical Notes

Continued on page 9

ForgottenGeniusPlease join us to view theNOVA documentary on Dr.Percy Julian and discuss hislife and achievementsFriday, April 13, 20071:30 pmBridgewater State CollegeMoakley CenterCo-sponsored by the BSC ChemistryDepartment, Center for the Advance-ment of Science Education, and theAmerican Chemical SocietyA discussion on the life of Dr. Julian,and the opportunities and challengesfor minority scientists will be led byDr. James Shoffner from the AmericanChemical Society Department ofDiversity Programs. Please RSVP to Dr. Steve Haefnershaefner(at)bridgew.edu508-531-2984 ◆◆


In the fall of 2007, Mar garet E.Greenslade will begin as an AssistantProfessor in the Department of Chem-istry at the University of New Hamp-shire. Her research will revolve aroundphysical and chemical transformationsof aerosols observed from an opticaland morphological point of view. Ex-perimental work, both in the laboratoryand the field, will be complementedwith theory and model studies. ◆◆

UNH Faculty Margaret E. Greenslade JoinsFaculty at UNHB.A., 1998, BrynMawr CollegePh.D., 2005, Univer-sity of PennsylvaniaResearch Scientist,2005-present, Cooperative Institute forResearch in Environmental Science(CIRES) at University of Colorado,Boulder and an affiliate of the NationalOceanic and Atmospheric Administra-tion (NOAA)

Lecture Platform Speaker at the Chau -tauqua Institution and selected for theDistinguished Faculty AchievementAward at the University of Michigan.In 2001 he was elected to the Ameri-can Academy of Arts and Sciences andbecame a fellow of the American Asso-ciation for the Advancement of Sci-ence. In 2004 he was the recipient theHarrison Howe Award of the AmericanChemical Society. He was elected tothe National Academy of Sciences in2006. In 2007 he will receive theRepligen Award of the ACS Divisionof Biological Chemistry.

He is a member of the AmericanChemical Society and the AmericanSociety for Biochemistry and Molecu-lar Biology. He currently serves on theBoard of Editors of ACS ChemicalBiology and on the editorial boards ofa number of other journals. He is aconsultant for a number of pharmaceu -tical companies and has served on thescientific advisory boards ofNitroMed. Inc. and Oxon Medica Inc.He is a member of the Fredonia Col-lege Foundation Board of Directors.

He lives with his wife, MargaretGutowski, and son in Berkeley, Cali-fornia. ◆◆

BiographyContinued from page 8

The Nucleus Newsletter special edition

American Chemical Society’sNational Meeting in August

Why advertise in this issue?


We therefore decided to purify avidin from inclusionbodies as we had done previously with streptavidin.1 Inorder to do this, the bacterial leader originally engineeredonto the avidin had to be removed through site-directedmutagenesis. The wild-type avidin without the bacterialleader was smaller by 78 base pairs and there was a visibleshift in product size when visualized on an agarose gelalongside the wild-type construct. Once the leader wasremoved and the sequence confirmed, we began expressingthe protein in inclusion bodies.Charge mutant avidin

In the process of testing the wild-type avidin purifiedfrom the inclusion bodies, we observed that the tetramer didnot enter the separating gel during SDS-PAGE analysis, butinstead became immobilized in the stacking gel. It isreported6 that making a reduced charge mutant of avidinallows for better tetramer visualization on SDS-PAGE andso we made a series of 4 mutations to change surface char geresidues and reduce the pI. Additionally, lowering the pImay reduce stickiness when using avidin to label cell sur -face proteins. The following mutations were made: R122A,R124A, R2A, K3E in two rounds of mutagenesis. Both thedouble mutant (R122A, R124A) and the quadruple mutant(R122A, R124A, R2A, K3E) were functional, as determinedby testing with a biotin-4-fluorescein assay (Fig. 3).

When run on a gel, we expected to visualize tetramer ,however, this was not the case. It appears as though muchof the protein is monomeric due to misfolding and work isstill being done to optimize the re-fold conditions and maxi -mize tetramer yield. We utilized a new loading buffer con-taining no DTT to maintain disulfide bonds andsupplemented the refold buffer with 0.5M Arginine (0.2MNaHCO3, 0.5mM GSSG, 1 mM GSH) 7 and this has made asmall impact on tetramer formation (Fig. 5). 5mM DTTwas added fresh to the guanidinium hydrochloride toencourage correct disulfide bond formation. Work is still in

progress to recover more tetramer and more charge muta-tions may be made at a later date.Engineering “dead” avidin

Based on the mutations made in streptavidin (N23A,S27D, S45A) which all lie within the binding site ( Fig. 4)8,analogous mutations were made in avidin (N12A, S16D,T35A).

Site-directed mutagenesis was performed with primersdesigned to introduce the desired point mutations. The muta-genesis was performed in two rounds, the first round intro -ducing N12A and S16D and the second introducing T35A.The protein was purified using the modified renaturationbuffer containing 0.5M Arginine and the preliminary resultsshow the presence of a small amount of tetramer ( Fig. 5).Using the biotin-4 fluorescein assay to determine activity, thedouble mutant (N12A, S16D) shows little to no biotin bind -ing (Fig. 6). The triple mutant (N12A, S16D, T35A) wasalso cloned and sequenced, but was unable to fold properly.

The extinction coefficient of avidin was based on theEdelhoch method, is described by Pace.9 The extinctioncoefficient at 280 nm for the non-glycosylated form of avidinwas calculated as 22,125 M-1cm-1 per subunit in water, and as22,665 M-1cm-1 in guanidinium hydrochloride. These valuesagree with Kulomaa’s published value4 of 24,280 M-1cm-1.

During the course of the project, “dead” avidin and thecharge mutant avidin were cloned, purified and tested fortheir abilities to bind biotin. For the future, refolding condi -tions for both wild type and mutant avidin will be explored,which we hope will maximize tetramer yield. Eventually,we hope to produce a monovalent avidin by combining the“alive” and “dead” avidin in dif ferent molar ratios followed

Summer ScholarContinued from page 2

Figure 3

Figure 4


by purification on a Ni-NTA column in much the same waythat monovalent streptavidin is produced.Acknowledgements

I would like to thank the Northeastern Section of theAmerican Chemical Society for awarding me the JamesFlack Norris and Theodore William Richards UndergraduateSummer Scholarship. The scholarship was instrumental inallowing me to pursue a valuable research experience. Iwould also like to thank Dr. Mark Howarth, with whom Iworked very closely on this project, for his guidance, Profes-sor Alice Ting for allowing me the opportunity to spend thesummer as a member of her group, and the members of theTing lab for all their help and support.References1 Howarth, M., Chinnapen, D., Gerrow, K., Dorrrestein, P.C., Grandy,M.R., Kelleher, N.L, El-Husseini, A.& Ting, A.Y. A monovalentstreptavidin with a single femtomolar biotin binding site. Nat. Meth-ods. 3, 267-273 (2006).

Figure 6

Figure 5

4th AnnualWomen Chemists Committee

and Northeastern Section

Golf Tournament (held in conjunction with the 234th

National ACS meeting in Boston, MA)All proceeds from this tournament

support WCC and NESACS programs

August 22, 2007Golf - 2 pm

Buffet Dinner - 7 pmAwards - 8 pm

Brookline Golf Club at Putterham Meadows

Cost: $100 per golferOr $400 per foursome

Your entry fee covers:Best ball scramble, greens fee, cart, prizes (includinglongest drive for men and women, closest to the pin, andfirst, second, and third places), and dinner after golf(burgers, hot dogs, salads, etc.).Bus transportation will be available for a nominalcharge.

Hole Sponsorships are available at several levels:

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For reservations send your check to:Marilou Cashman23 Cottage Street, Natick, MA 01760Mcash0953(at)aol.comPlease include all golfers names and emailaddresses.

Continued on page 12

In 1985 an inquiry was made as towhether the Section would wish tohonor a former leader of the Northeast-ern Section. The Esselen family pro-posed to donate a sum of money toprovide for an award in the memory ofGustavus John Esselen II, Chairman in1922 and 1923, and a member of theACS Board of Directors for manyyears. In 1948, Dr. Esselen received aspecial award, the James Flack NorrisHonor Scroll, “as the person who hasdone most to advance the interests ofthe Northeastern Section.” A commit-tee consisting of William O. Foye, Tru-man S. Light, Arthur S. Obermayer,and Myron S. Simon, Section Chair-man, met with Esselen’s son, GustavusJ. Esselen III, and recommended to theBoard of Directors that the Sectionaccept the offer. The committee andMr. Esselen agreed that the awardshould not be in a specific field ofchemistry, but instead should have thespecial purpose of emphasizing thepositive values of chemistry tomankind. In light of the climate of theday, with the disaster of Bhopal onevery chemist’s mind and the public

receiving nothing but negative storiesabout chemistry, this was to be a smallstep toward establishing a balance.

Mr. Esselen proposed to add abronze medal to the monetary award.A prominent sculptor from Newton,Massachusetts, Lloyd Lillie, wasselected to prepare the design whichwas then approved by members of theEsselen family. The fact that Dr. Esse-len had done much work in plasticsduring his career led his son to proposethat the bronze medal be imbedded in ablock of clear plastic. This was done,giving a very distinctive addition to theceremonial presentation.

The first presentation of the Gus-tavus John Esselen Award for Chem-istry in the Public Interest was made in1987 to F. Sherwood Rowland andMario J. Molina for their work on thechemical processes which weredestroying the stratospheric ozonelayer, explaining the formation of theAntarctic Ozone Hole. Since then, theaward has been given to chemists inseveral fields of chemistry and hasbecome a much coveted prize.

This is an edited version of a moredetailed history of the origins of theEsselen Award. A comprehensive his-tory written by Myron S. Simon wasmost recently published on page 10 ofthe May 2006 issue of The Nucleus. ◆◆

The Gustavus John Esselen Award for Chemistry in the Public Interest


Chair-Elect Dr. E. Joseph Billo

SecretaryDr. Michael Singer

Trustee Dr. Esther A. H. Hopkins

Councilor/Alt. CouncilorDr. Mukund ChorghadeDr. David CunninghamDr. Timothy B. FrigoDr. Mark FroimowitzDr. Thomas GilbertDr. Robert LichterDr. Pamela NagafujiDr. Eriks RoznersDr. Michael Singer

Director-at-LargeMs. Laila DafikMr. Steve Lantos

Nominating CommitteeDr. David CunninghamDr. Jerry JasinskiDr. Pamela NagafujiDr. Dorothy J. Phillips

Esselen Award CommitteeDr. Sean LuDr. Alfred Viola

Richards Medal CommitteeDr. Peter Jacobi Dr. Barry KargerDr. Daniel NoceraDr. Dagmar Ringe ◆◆

NESACS Candidates for2007

2 Chen, I., Howarth, M., Lin, W., & Ting,A.Y. Site-specific labeling of cell surfaceproteins with biophysical probes usingbiotin ligase. Nat. Methods. 2, 99-104(2005).

3 Barth, S., Huhn, M., Matthey, B., Lkimka,A., Galinski, E.A., and Engert, (2000) A.Compatible-Solute-Supported PeriplasmicExpression of Functional RecombinantProteins under Stress Conditions. Appliedand Environmental Microbiology.. 66,1572-1579.

4 Hytönen, V.P., Laitinen, O.H.,, Airenne, T.T., Kidron, H., Meltola, N.J., Prokka, E.J.,Hörha, J. Paldanius, T., Määttä, J.A.E.,Nordlund, H.R., Johnson, M.S., Salminen,T.A., Airenne, K.J., Ylä-Herttuala, S., andKulomaa, M.S. (2004). Efficient produc-tion of active chicken avidin using a bacte -rial signal peptide in Escherichia coli.Biochem J. 384, 385-390.

6 Marttila, A.T., Airenne, K.J., Laitinen,O.H., Kulik, T., Bayer, E.A., Wilchek, M.,and Kulomaa, M.S. (1998). Engineering ofchicken avidin: a progressive series ofreduced charge mutants. FEBS Letters 441,313-317.

7 Nardone, E., Rosano, C., Santambrogio, P.,Curnis, F., Corti, A., Magni, F., Siccardi, A.G., Paganelli, G., Losso, R., Apreda B.,Bolognesi, M., Sidoli, A., and Arosio, P.(1998) Biochemical characterization andcrystal structure of a recombinant henavidin and its acidic mutant expressed inEscherichia coli. Eur. J. Biochem. 256,453-460.

8 Eisenberg-Domovich, Y., Hytönen, V.P.,Wilchek, M., Bayer, E.A., Kulomaa, M.S.and Livnah, O. (2005) High resolutioncrystal structure of an avidin-related pro-tein: insight into high-affinity biotin bind-ing and protein stability. Acta Cryst. 61,528-538.

9 Pace, C.N., Vajdos, F., Fee, L., Grimsley,G., and Gray, T. (1995) How to measureand predict the molar absorption coeffi-cient of a protein. Protein Science. 4, 2411-2423. ◆◆

Summer ScholarContinued from page 11


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Check the NESACS Homepagefor late additions:http://www.NESACS.orgNote also the Chemistry Department webpages for travel directions and updates.These include:http://chemserv.bc.edu/seminar.htmlhttp://www.bu.edu/chemistry/events/http://www.chem.brandeis.edu/colloquium.shtmlhttp://www-chem.harvard.edu/events/http://web.mit.edu/chemistry/www.chem.neu.edu/web/calendar/index.htmlhttp://chem.tufts.edu/seminars.html [CHEM.]http://ase.tufts.edu/chemical/seminar.htm

[CHEM. ENGG.]http://www.chem.umb.edu/www.umassd.edu/cas/chemistry/seminars.cfmwww.uml.edu/Dept/Chemistry/speakers.htmlhttp://www.unh.edu/chemistry/seminars.html

Apr 3Kim R. Dunbar(Texas A & M University)TBAUNH, Room L10311:10 amProf. Antonio M. Echavarren, Institut Catalàd’Investigació Químa, Spain“The Mechanistic Puzzle of Gold-CatalyzedCyclizations of Enynes and Beyond”Boston College, Merkert 1304:00 pm

Apr 4 Dr. D. Venkataraman (U. Mass Amherst)TBAU. Mass Dartmouth, Building Group II, Rm. 115 4:00 pm

Apr 5Prof. Chang Y. Rhu (Rensselaer Polytechnic)“Polymer Adsorption into Nanopores and ItsApplications for Polymer HPLC”U. Mass. Lowell, Olney Hall Rm 2183:30 pm

Apr 9 Chad Rienstra (UIUC )“New Dimensions in Magic-Angle SpinningNMR of Membrane Proteins: Methods andApplications for Physical Chemistry andStructural Biology”MIT, 56-1144:30 pmEiichi Nakamura, (Univ. of TokyoTBAHarvard, Pfizer Lecture Hall 4:15 pm

Apr 10 Professor Rob Doyle (Syracuse Univ.)“Vitamin Bioconjugates for Drug Delivery” UNH, Room L10311:10 amProfessor Chuan He, (University of Chicago)TBABoston College, Merkert 1304:00 pmProf. Alanna Schepartz, (Yale University)TBATufts, Pearson Rm P-106 4:30 pm

Apr 11 Dr. Chuan He, (Univ. of Chicago)“Regulations of Virulence, Antibiotic Resistance,and Metal Ion Concentrations in Bacteria” Brandeis Univ., Gerstenzang 1223:45 pm

Apr 12Michelle Wang (Cornell)TBAHarvard, Pfizer Lecture Hall 4:00 pm

Apr 13Dr. James Shoffner (ACS Department ofDiversity Programs)“A discussion on the life of Dr. Percy Julian,

Forgotten Genius, and the opportunities andchallenges for minority scientist.” Bridgewater State College, Moakley Center1:30 pm RSVP to Dr. Steve [email protected]

Apr 16Dr. Ken Caulton (Indiana Univ.) “Spin States, Unsaturation, and Pi-Donation:Impact on Reactivity” Brandeis Univ., Gerstenzang 122 3:45 pm

Apr 17 Dr. Maureen Fagan (Smith College) “Synthesis and Reactivity of Palladium EnolateComplexes” UNH, Room L103 11:10 amProf. Samuel J. Danishefsky, (Sloan-KetteringInstitute & Columbia Univ.) TBABoston College, Merkert 130 4:00 pmProf. Rick van Duyne (Northwestern)“Molecular Plasmonics for Surface EnhancedSensing and Raman Spectroscopy”Tufts, Pearson Rm P-106 4:30 pm

Apr 19 Richard Mathies (UC Berkeley)Title: Femtosecond Stimulated RamanSpectroscopy Harvard / MIT Seminar SeriesMIT 56-1145:00 pm

Apr 23Dr. Shannon Stahl, (Univ. of Wisconsin)TBABrandeis Univ., Gerstenzang 1223:45 pm Tamar Seideman (Northwestern)TBAMIT, 56-114 4:30 pm

Apr 24 Professor Gregory Sotzing (U. Conn)“Nanolithography, Nanofibers and ConductingPolymers” UNH, Room L10311:10 amProfessor Anna K. Mapp, (U. Michigan)TBABoston College, Merkert 130 4:00 pm

Apr 26Prof. Afred Crosby (U. Mass Amherst)“Natures’s Instabilities: Inspiring MaterialsDesign and Characterization”U. Mass. Lowell, Olney Hall Rm 2183:30 pm

Apr 30Dr. J. M. Brown (Oxford Univ.) “Racemic Ligands in Catalytic AsymmetricSynthesis”Brandeis Univ., Gerstenzang 122 3:45 pm

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Did you know 17,000 copies of theSummer Nucleus will be printed and10,000 will be handed out to atten-dees at the Boston National ACSMeeting to be held in August 2007.

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yyyy Monthly Meeting Summer - NESACS · “Nontraditional Careers for Chemists: New Formulas in Chemistry,” Reviewed By Lynne A. O'Connell, Department of Chemistry, Boston College