DNA-protein conjugates are potentially repaired via proteolytic digestion to DNA-peptide conjugates. The latter have been modeled with the amino-terminal lysine of the peptide KWKK conjugated via a trimethylene linkage to the N 2-dG amine positioned in 5′-d(GCTAGCXAGTCC)-3′5′- d(GGACTCGCTAGC)-3′ (X = N2-dG-trimethylene link-KWKK). This linkage is a surrogate for the reversible linkage formed by the γ-OH-1,N2-propanodeoxyguanosine (γ-OH-PdG) adduct. This conjugated KWKK stabilizes the DNA. Amino acids K26, W27, K28, and K29 are in the minor groove. The W27 indolyl group does not intercalate into the DNA. The G7 N2 amine and the K26 N-terminal amine nitrogens are in the trans configuration with respect to the Cα or Cγ of the trimethylene tether, respectively. The structure of this DNA-KWKK conjugate is discussed in the context of its biological processing.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jul 27 2010|
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