DSSR-PyMOL cartoon-block schematics: PDB entry 1k8l

PDB-id

1k8l; DSSR-derived features in text and JSON formats

Class

DNA

Method

NMR

Summary

Xby6: an analog of ck14 containing 6 dithiophosphate groups

Reference

Volk DE, Yang X, Fennewald SM, King DJ, Bassett SE, Venkitachalam S, Herzog N, Luxon BA, Gorenstein DG (2002): "Solution structure and design of dithiophosphate backbone aptamers targeting transcription factor NF-kappaB." Bioorg.Chem., 30, 396-419. doi: 10.1016/S0045-2068(02)00510-2.

Abstract

A variety of monothio- and dithiosubstituted duplex aptamers targeting NF-kappaB have been synthesized and designed. The specificity and affinity of the dithioate aptamers of p50 and RelA(p65) NF-kappaB homodimers was determined by gel shift experiments. The NMR solution structures for several unmodified and dithioate backbone modified 14-base paired duplex aptamers have been determined by a hybrid, complete matrix (MORASS)/restrained molecular dynamics method. Structural perturbations of the dithioate substitutions support our hypothesis that the dithioate binds cations less tightly than phosphoryl groups. This increases the electrostatic repulsion across the B-form narrow minor groove and enlarges the minor groove, similar to that found in A-form duplexes. Structural analysis of modeled aptamer complexes with NF-kappaB homo- and heterodimers suggests that the dithioate backbone substitution can increase the aptamer's relative affinity to basic groups in proteins such as NF-kappaB by helping to "strip" the cations from the aptamer backbone.