Crystal structures of DNA:DNA and DNA:RNA duplexes containing 5-(N-aminohexyl)carbamoyl-modified uracils reveal the basis for properties as antigene and antisense molecules.

ABSTRACT: Oligonucleotides containing 5-(N-aminohexyl)carbamoyl-modified uracils have promising features for applications as antigene and antisense therapies. Relative to unmodified DNA, oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2'-deoxyuridine ((N)U) or 5-(N-aminohexyl)carbamoyl-2'-O-methyluridine ((N)U(m)), respectively exhibit increased binding affinity for DNA and RNA, and enhanced nuclease resistance. To understand the structural implications of (N)U and (N)U(m) substitutions, we have determined the X-ray crystal structures of DNA:DNA duplexes containing either (N)U or (N)U(m) and of DNA:RNA hybrid duplexes containing (N)U(m). The aminohexyl chains are fixed in the major groove through hydrogen bonds between the carbamoyl amino groups and the uracil O4 atoms. The terminal ammonium c

SUBMITTER: Juan EC 

PROVIDER: S-EPMC1874594 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature