CHO, YS ZHU, FC LUXON, BA GORENSTEIN, DG 2024-01-21T22:13:01Z 2024-01-21T22:13:01Z 2021-09-01 1993-12 0739-1102 https://pubs.kist.re.kr/handle/201004/145946 Assignment of the H-1 and P-31 NMR spectra of a phosphorodithioate modified oligonucleotide decamer duplex, d(CGCTTpS(2)AAGCG)(2) (10-mer-S; a site of dithioate substitution is designated with the symbols pS(2)), was achieved by two-dimensional homonuclear TOCSY, NOESY and H-1-P-31 Pure Absorption phase Constant time (PAC) heteronuclear correlation spectroscopy. In contrast to the parent palindromic decamer sequence (1) which has been shown to exist entirely in the duplex B-DNA conformation under comparable conditions (100 mM KCl), the dithiophosphate analogue forms a hairpin loop. However, the duplex form of the dithioate oligonucleotide can be stabilized at lower temperatures, higher salt and strand concentration. The solution structure of the decamer duplex was calculated by an iterative hybrid relaxation matrix method (MORASS) combined with 2D NOESY-distance restrained molecular dynamics. These backbone modified compounds, potentially attractive antisense oligonucleotide agents, are often assumed to possess similar structure as the parent nucleic acid complex. Importantly, the refined structure of the phosphorodithioate duplex shows a significant deviation from the parent unmodified, phosphoryl duplex. An overall bend and unwinding in the phosphorodithioate duplex is observed. The structural distortion of the phosphorodithioate duplex was confirmed by comparison of helicoidal parameters and groove dimensions. Especially, the helical twists of the phosphorodithioate decamer deviate significantly from the parent phosphoryl decamer. The minor groove width of phosphorodithioate duplex 10-mer-S varies between 8.4 and 13.3 Angstrom which is much wider than those of the p arent phosphoryl decamer d(CGCTTAAGCG)(2)(4.2 similar to 9.4 Angstrom). The larger minor groove width of 10-mer-S duplex contributes to the unwinding of the backbone and indicates that the duplex has an overall A-DNA-like conformation in the region surrounding the dithiophosphate modification. English ADENINE PRESS INC PURE-ABSORPTION-PHASE HUMAN IMMUNODEFICIENCY VIRUS RELAXATION MATRIX PROCEDURE OLIGODEOXYRIBONUCLEOTIDE DUPLEX 2-DIMENSIONAL H-1 PROTON RESONANCES ASSIGNMENT OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE SPECTROSCOPY 2D H-1 AND P-31 NMR-SPECTRA AND DISTORTED A-DNA-LIKE DUPLEX STRUCTURE OF A PHOSPHORODITHIOATE OLIGONUCLEOTIDE Article 10.1080/07391102.1993.10508023 1 JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, v.11, no.3, pp.685 - 702 JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS 11 3 685 702 scie scopus A1993MQ36800015 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article PURE-ABSORPTION-PHASE HUMAN IMMUNODEFICIENCY VIRUS RELAXATION MATRIX PROCEDURE OLIGODEOXYRIBONUCLEOTIDE DUPLEX 2-DIMENSIONAL H-1 PROTON RESONANCES ASSIGNMENT OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE SPECTROSCOPY phosphorodithioate oligonucleotide two-dimensional homonuclear TOCSY NOESY ¹H-³¹P heteronuclear correlation spectroscopy