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From DNA to Protein
Transcription
Translation
The Genetic Code
Sickle Cell Anemia
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Barton and co-workers showed that the electron transfer was not sufficiently sensitive to the dynamic motions of a G-A mismatch to perturb the electroniccoupling through the bases; hence, the mismatch was not detected.
To solve this problem, they used an electrocatalytic system that coupled ferricyanide as an oxidant to recycle the reduced form of MB (leucomethylene blue) back to MB. The electrocatalysis amplified the sensitivity to the base motions and allowed the G-A mismatch to be detected.
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Gooding et al. have used 2,6-Disulfonic Acid Anthraquinone (AQDS) as intercalator. AQDS is a anionic intercalator :
Negative Intercalators
The greater sensitivity of the AQDS to electronic perturbations could infer that the AQDS is less well electronically coupled with the base stack than the MB, as inferred by the low rate of electron transfer.
Anal. Chem. 2003, 75, 3845.18
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Anal. Chem. 2003, 75, 3845.21
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Sensors and Actuators B, 111–112, 2005, 515.
If there was a mismatch in the duplex, the electron transfer
was either completely diminished or greatly reduced.
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Charge Migration Through theDNA Double Helix
Introduction
• The charge-transport in DNA have intrigued:• chemists• Physicists• biologists
• The striking similarity of the π-stacked array of DNA bases to π-stacked solid-state conductors has prompted the suggestion that DNA might efficiently facilitate charge transport.
Charge transfer in DNA
Charge mobility in DNA has consequences for:
DNA damage, which dictates biological damage from: Radiation UV, Light Chemicals
Nanoscale electronic devices
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Charge Transfer through DNA
Less than a decade after discovering of structural features of DNA
double helix, the first experiments to answer how charge can be
transported through DNA chains were carried out.
ButThis question is still debated-Does DNA act as: An insulator,
A semiconductor
Or a molecular wire???
Insulators, semiconductors and conductors
Energy
Insulator
Conductionband
Valenceband
SemiconductorConductor
Electron
Electron
Hole
The early years
Eley and Spivey (1962)*:Conduction in DNA arises from thermally excited electrons on the paired bases, which traverse along the -stacks of the DNA bases
Gregoli, Olast and Bertinchamps (1982)**:
Charge migration occurs via the stacked bases, but may be hindered by interfering factors **
Radiat. Res. 89*Trans. Farad. Soc. 58
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Photoinduced Methods
h
DonorAcceptor e-
F. D. Lewis, et al., Acc. Chem. Res. 34, 159, 2001.H-A. Wagenknecht Angew. Chem. Int. Ed. 42, 2454, 2003G. B. Schuster, Acc. Chem. Res. 33, 253, 2000.
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Key Steps
1. Covalent labeling of the DNA with redox-active
probes.
2. Photochemical initiation of the charge transfer
process.
3. Spectroscopic or electrochemical detection of the
charge transfer processes or analysis of irreversible
DNA products yielded by the charge transfer reaction.
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• Charge transport can occur through DNA over at least short distance
• Positive charge (hole) transport:Nucleobase guanine is the carrier of positive charge.
• Electron transport:
Thymine and cytosine are the charge carriers?
Hole or electron??????
Page 24
Photoinduced transfer (1)
Donor[Ru(phen’)2dppz] 2+
Acceptor[Rh(phi)2phen’] 3+
Murphy et al. Science 262 (1993)
15 base pairs
Hybridization of DNA strands, each intercalated with metal complex
Ru-complex luminesces, but not when connected to Rh-complex via DNA
DNA is a conductor
Means of transfer
Tunneling(independent of temperature)
Boon and Barton (illustrations)Curr. Opin. Struct. Biol. 12 (2002)
Hopping(dependent of temperature)
kct=k0e-R
kct=k0(T)N-
Grozema et al. (theory)J. Am. Chem. Soc. 122 (2000)