Open AccessCyclic phosphates of some antiviral acyclonucleosides: relationship between conformation and substrate/inhibitor properties in some enzyme systems.
Author(s) -
J M Cieśla,
R Stolarski,
David Shugar
Publication year - 1993
Publication title -
acta biochimica polonica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.452
H-Index - 78
eISSN - 1734-154X
pISSN - 0001-527X
DOI - 10.18388/abp.1993_4826
Subject(s) - guanine , chemistry , stereochemistry , nuclease , enzyme , phosphodiesterase , substrate (aquarium) , ring (chemistry) , phosphate , hydroxymethyl , biochemistry , nucleotide , organic chemistry , biology , gene , ecology
Solution conformations, and substrate/inhibitor properties towards several phosphodiesterases and other nucleolytic enzymes, have been investigated for the cyclic phosphates of various acyclonucleosides, some with known antiviral activity, including 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and its carbocyclic congener, 9-(3,4-dihydroxybutyl)guanine (DHBG),9-[4-hydroxy-2-(hydroxymethyl)- butyl]-guanine (2HM-HBG), and 9-(2,3-dihydroxypropyl)guanine (HPG). Conformations of the cyclic phosphate rings were derived from analysis of the 1H-1H and 1H-31P vicinal coupling constants in the 1H n.m.r. spectra, subsequently optimalized by minimalization of the internal energy. The resulting structures were examined with respect to their ability to recognize various specific phosphodiesterases and nucleases, and some structural parameters were delineated for acyclonucleotide interactions. Qualitative data are presented for inhibitory properties of the acyclonucleoside cyclic phosphates, and, in those instances where they were substrates, kinetic constants were evaluated. An unusual finding was the apparent ability of nuclease P1 to hydrolyse a five-membered cyclic phosphate ring of an acyclonucleoside.