Base pair stability of 8-chloro- and 8-iodo-2′-deoxyguanosine opposite 2′-deoxycytidine:: Implications regarding the bioactivity of 8-oxo-2′-deoxyguanosine

8-Oxo-2′-deoxyguanosine (OdG) is an abundant and promutagenic damaged nucleotide that has been linked to aging and disease. To gain insight into the alternate base pairings of OdG, 8-chloro- and 8-iodo-2′-deoxyguanosine were incorporated into oligonucleotides and, along with 2′-deoxyguanosine and 8-bromo-2′-deoxyguanosine, were tested for their stability in base pairs opposite dC. We found a strong correlation between increased atomic radius and bond length at C8 and decreased base pair stability. These findings along with NMR studies on the base conformation of the corresponding nucleosides support the theory that the steric bulk of the 8-oxygen plays a role in OdG mutation and disease. Copyright © 2005 American Chemical Society.