Matches in SemOpenAlex for { <https://semopenalex.org/work/W1969788448> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W1969788448 endingPage "8517" @default.
- W1969788448 startingPage "8511" @default.
- W1969788448 abstract "The X-ray crystal structures of 12 substrate-based peptidic inhibitors bound in the active site of the aspartyl protease, HIV-1 protease, have been compared. The inhibitor-binding modes of these inhibitors are remarkably similar despite their structural diversity and conformational flexibility. This prompted the design of a bicyclic peptidomimetic inhibitor 13 with macrocyclic components in constrained conformations that are preorganized for receptor-binding. This inhibitor is a consensus conformational mimic of the protease-bound inhibitor structures with superior properties to peptides, including stability to acid and peptidases as well as antiviral activity. Each of its 15- and 16-membered rings, formed through side-chain to backbone condensation, contains two proteolytically resistant amide bonds and either isoleucine or valine linked via a short aliphatic spacer to tyrosine. The two cycles are connected by a hydroxyethylamine transition state isostere. Molecular modeling and NMR studies indicate that each macrocycle is a highly constrained structural mimic of tripeptide components of linear peptide substrates/inhibitors of HIV-1 protease. Thus the bicyclic peptidomimetic superimposes upon and structurally mimics acyclic hexapeptide inhibitors and their analogues. This results in functional mimicry, as demonstrated by comparable inhibition of HIV-1 protease by acyclic and cyclic molecules at nanomolar concentrations. The rational design of cycles which fix receptor-bound conformations of these bioactive peptides has potential applications for the structural mimicry of other bioactive peptides and may facilitate rational drug design." @default.
- W1969788448 created "2016-06-24" @default.
- W1969788448 creator A5009112740 @default.
- W1969788448 creator A5019632866 @default.
- W1969788448 creator A5020486039 @default.
- W1969788448 creator A5021768732 @default.
- W1969788448 creator A5053439487 @default.
- W1969788448 creator A5072274976 @default.
- W1969788448 date "1996-01-01" @default.
- W1969788448 modified "2023-09-23" @default.
- W1969788448 title "A Novel Bicyclic Enzyme Inhibitor as a Consensus Peptidomimetic for the Receptor-Bound Conformations of 12 Peptidic Inhibitors of HIV-1 Protease" @default.
- W1969788448 cites W1965349185 @default.
- W1969788448 cites W1992651835 @default.
- W1969788448 cites W2060879531 @default.
- W1969788448 cites W2069366448 @default.
- W1969788448 cites W2069961994 @default.
- W1969788448 cites W2086003834 @default.
- W1969788448 cites W2087876594 @default.
- W1969788448 cites W2091797397 @default.
- W1969788448 cites W2157809663 @default.
- W1969788448 cites W2160276605 @default.
- W1969788448 cites W2485563582 @default.
- W1969788448 cites W4235305170 @default.
- W1969788448 cites W4252671483 @default.
- W1969788448 doi "https://doi.org/10.1021/ja960433v" @default.
- W1969788448 hasPublicationYear "1996" @default.
- W1969788448 type Work @default.
- W1969788448 sameAs 1969788448 @default.
- W1969788448 citedByCount "35" @default.
- W1969788448 countsByYear W19697884482014 @default.
- W1969788448 countsByYear W19697884482016 @default.
- W1969788448 countsByYear W19697884482018 @default.
- W1969788448 countsByYear W19697884482020 @default.
- W1969788448 countsByYear W19697884482023 @default.
- W1969788448 crossrefType "journal-article" @default.
- W1969788448 hasAuthorship W1969788448A5009112740 @default.
- W1969788448 hasAuthorship W1969788448A5019632866 @default.
- W1969788448 hasAuthorship W1969788448A5020486039 @default.
- W1969788448 hasAuthorship W1969788448A5021768732 @default.
- W1969788448 hasAuthorship W1969788448A5053439487 @default.
- W1969788448 hasAuthorship W1969788448A5072274976 @default.
- W1969788448 hasConcept C124790011 @default.
- W1969788448 hasConcept C13053905 @default.
- W1969788448 hasConcept C167392928 @default.
- W1969788448 hasConcept C180000673 @default.
- W1969788448 hasConcept C181199279 @default.
- W1969788448 hasConcept C185592680 @default.
- W1969788448 hasConcept C24961977 @default.
- W1969788448 hasConcept C2776714187 @default.
- W1969788448 hasConcept C2777583353 @default.
- W1969788448 hasConcept C2779281246 @default.
- W1969788448 hasConcept C41183919 @default.
- W1969788448 hasConcept C53105671 @default.
- W1969788448 hasConcept C54355233 @default.
- W1969788448 hasConcept C55493867 @default.
- W1969788448 hasConcept C71240020 @default.
- W1969788448 hasConcept C86803240 @default.
- W1969788448 hasConceptScore W1969788448C124790011 @default.
- W1969788448 hasConceptScore W1969788448C13053905 @default.
- W1969788448 hasConceptScore W1969788448C167392928 @default.
- W1969788448 hasConceptScore W1969788448C180000673 @default.
- W1969788448 hasConceptScore W1969788448C181199279 @default.
- W1969788448 hasConceptScore W1969788448C185592680 @default.
- W1969788448 hasConceptScore W1969788448C24961977 @default.
- W1969788448 hasConceptScore W1969788448C2776714187 @default.
- W1969788448 hasConceptScore W1969788448C2777583353 @default.
- W1969788448 hasConceptScore W1969788448C2779281246 @default.
- W1969788448 hasConceptScore W1969788448C41183919 @default.
- W1969788448 hasConceptScore W1969788448C53105671 @default.
- W1969788448 hasConceptScore W1969788448C54355233 @default.
- W1969788448 hasConceptScore W1969788448C55493867 @default.
- W1969788448 hasConceptScore W1969788448C71240020 @default.
- W1969788448 hasConceptScore W1969788448C86803240 @default.
- W1969788448 hasIssue "36" @default.
- W1969788448 hasLocation W19697884481 @default.
- W1969788448 hasOpenAccess W1969788448 @default.
- W1969788448 hasPrimaryLocation W19697884481 @default.
- W1969788448 hasRelatedWork W1969788448 @default.
- W1969788448 hasRelatedWork W2013520316 @default.
- W1969788448 hasRelatedWork W2033261209 @default.
- W1969788448 hasRelatedWork W2056005890 @default.
- W1969788448 hasRelatedWork W2060879531 @default.
- W1969788448 hasRelatedWork W2086720310 @default.
- W1969788448 hasRelatedWork W2134418875 @default.
- W1969788448 hasRelatedWork W2154196106 @default.
- W1969788448 hasRelatedWork W2506150632 @default.
- W1969788448 hasRelatedWork W4230154845 @default.
- W1969788448 hasVolume "118" @default.
- W1969788448 isParatext "false" @default.
- W1969788448 isRetracted "false" @default.
- W1969788448 magId "1969788448" @default.
- W1969788448 workType "article" @default.