Open AccessInterstrand DNA Cross-Links Derived from Reaction of a 2-Aminopurine Residue with an Abasic Site
Author(s) -
Maryam Imani Nejad,
Nathan E. Price,
Tuhin Haldar,
Calvin D. Lewis,
Yinsheng Wang,
Kent S. Gates
Publication year - 2019
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.9b00208
Subject(s) - duplex (building) , ap site , footprinting , dna , chemistry , residue (chemistry) , nucleobase , combinatorial chemistry , stereochemistry , biochemistry , dna damage , base sequence
Efficient methods for the site-specific installation of structurally defined interstrand cross-links in duplex DNA may be useful in a wide variety of fields. The work described here developed a high-yield synthesis of chemically stable interstrand cross-links resulting from a reductive amination reaction between an abasic site and the noncanonical nucleobase 2-aminopurine in duplex DNA. Results from footprinting, liquid chromatography-mass spectrometry, and stability studies support the formation of an N 2 -alkylamine attachment between the 2-aminopurine residue and the Ap site. The reaction performs best when the 2-aminopurine residue on the opposing strand is offset 1 nt to the 5'-side of the abasic site. The cross-link confers substantial resistance to thermal denaturation (melting). The cross-linking reaction is fast (complete in 4 h), employs only commercially available reagents, and can be used to generate cross-linked duplexes in sufficient quantities for biophysical, structural, and DNA repair studies.