FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2012108232> ?p ?o ?g. }

• W2012108232 endingPage "947" @default.
• W2012108232 startingPage "937" @default.
• W2012108232 abstract "Potential advantages of C2-symmetric inhibitors designed for the symmetric HIV-1 protease include high selectivity, potency, stability, and bioavailability. Pseudo-C2-symmetric monools and C2-symmetric diols, containing central hydroxymethylene and (R,R)-dihydroxyethylene moieties flanked by a variety of hydrophobic P1/P1' side chains, were studied as HIV-1 protease inhibitors. The monools and diols were synthesized in 8-10 steps from D-(+)-arabitol and D-(+)-mannitol, respectively. Monools with ethyl or isobutyl P1/P1' side chains were weak inhibitors of recombinant HIV-1 protease (Ki > 10 microM), while benzyl P1/P1' side chains afforded a moderately potent inhibitor (apparent Ki = 230 nM). Diols were 100-10,000x more potent than analogous monools, and a wider range of P1/P1' side chains led to potent inhibition. Both classes of compounds exhibited lower apparent Ki values under high-salt conditions. Surprisingly, monool and diol HIV-1 protease inhibitors were potent inhibitors of porcine pepsin, a prototypical asymmetric monomeric aspartic protease. These results were evaluated in the context of the pseudosymmetric structure of monomeric aspartic proteases and their evolutionary kinship with the retroviral proteases. The X-ray crystal structure of HIV-1 protease complexed with a symmetric diol was determined at 2.6 A. Contrary to expectations, the diol binds the protease asymmetrically and exhibits 2-fold disorder in the electron density map. Molecular dynamics simulations were conducted beginning with asymmetric and symmetric HIV-1 protease/inhibitor model complexes. A more stable trajectory resulted from the asymmetric complex, in agreement with the observed asymmetric binding mode. A simple four-point model was used to argue more generally that van der Waals and electrostatic force fields can commonly lead to an asymmetric association between symmetric molecules." @default.
• W2012108232 created "2016-06-24" @default.
• W2012108232 creator A5000913274 @default.
• W2012108232 creator A5008377805 @default.
• W2012108232 creator A5021850924 @default.
• W2012108232 creator A5037778058 @default.
• W2012108232 creator A5047649241 @default.
• W2012108232 creator A5055743310 @default.
• W2012108232 creator A5068704464 @default.
• W2012108232 creator A5075134344 @default.
• W2012108232 date "1993-01-26" @default.
• W2012108232 modified "2023-10-16" @default.
• W2012108232 title "A symmetric inhibitor binds HIV-1 protease asymmetrically" @default.
• W2012108232 cites W1514209943 @default.
• W2012108232 cites W1608052268 @default.
• W2012108232 cites W1637218542 @default.
• W2012108232 cites W1965349185 @default.
• W2012108232 cites W1967279802 @default.
• W2012108232 cites W1969071470 @default.
• W2012108232 cites W1975914851 @default.
• W2012108232 cites W1979853120 @default.
• W2012108232 cites W1985469117 @default.
• W2012108232 cites W1987688509 @default.
• W2012108232 cites W1995597071 @default.
• W2012108232 cites W1999176468 @default.
• W2012108232 cites W2002324478 @default.
• W2012108232 cites W2006327082 @default.
• W2012108232 cites W2010633578 @default.
• W2012108232 cites W2017607746 @default.
• W2012108232 cites W2028570880 @default.
• W2012108232 cites W2028659951 @default.
• W2012108232 cites W2035241906 @default.
• W2012108232 cites W2035286938 @default.
• W2012108232 cites W2039166001 @default.
• W2012108232 cites W2056633621 @default.
• W2012108232 cites W2057744044 @default.
• W2012108232 cites W2058155604 @default.
• W2012108232 cites W2058898122 @default.
• W2012108232 cites W2063145032 @default.
• W2012108232 cites W2069366448 @default.
• W2012108232 cites W2070368233 @default.
• W2012108232 cites W2085318243 @default.
• W2012108232 cites W2086003834 @default.
• W2012108232 cites W2087876594 @default.
• W2012108232 cites W2089657765 @default.
• W2012108232 cites W2092093169 @default.
• W2012108232 cites W2097410498 @default.
• W2012108232 cites W2102537419 @default.
• W2012108232 cites W2112889378 @default.
• W2012108232 cites W2114742412 @default.
• W2012108232 cites W2132666819 @default.
• W2012108232 cites W2155524113 @default.
• W2012108232 cites W2155894418 @default.
• W2012108232 cites W2160276605 @default.
• W2012108232 cites W2169655668 @default.
• W2012108232 cites W2316906870 @default.
• W2012108232 cites W240501384 @default.
• W2012108232 cites W2951545754 @default.
• W2012108232 cites W4252671483 @default.
• W2012108232 doi "https://doi.org/10.1021/bi00054a027" @default.
• W2012108232 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/8422397" @default.
• W2012108232 hasPublicationYear "1993" @default.
• W2012108232 type Work @default.
• W2012108232 sameAs 2012108232 @default.
• W2012108232 citedByCount "67" @default.
• W2012108232 countsByYear W20121082322012 @default.
• W2012108232 countsByYear W20121082322013 @default.
• W2012108232 countsByYear W20121082322014 @default.
• W2012108232 countsByYear W20121082322018 @default.
• W2012108232 countsByYear W20121082322019 @default.
• W2012108232 crossrefType "journal-article" @default.
• W2012108232 hasAuthorship W2012108232A5000913274 @default.
• W2012108232 hasAuthorship W2012108232A5008377805 @default.
• W2012108232 hasAuthorship W2012108232A5021850924 @default.
• W2012108232 hasAuthorship W2012108232A5037778058 @default.
• W2012108232 hasAuthorship W2012108232A5047649241 @default.
• W2012108232 hasAuthorship W2012108232A5055743310 @default.
• W2012108232 hasAuthorship W2012108232A5068704464 @default.
• W2012108232 hasAuthorship W2012108232A5075134344 @default.
• W2012108232 hasConcept C142462285 @default.
• W2012108232 hasConcept C159047783 @default.
• W2012108232 hasConcept C178790620 @default.
• W2012108232 hasConcept C181199279 @default.
• W2012108232 hasConcept C182220744 @default.
• W2012108232 hasConcept C185592680 @default.
• W2012108232 hasConcept C204921945 @default.
• W2012108232 hasConcept C2776714187 @default.
• W2012108232 hasConcept C2777583353 @default.
• W2012108232 hasConcept C2781143361 @default.
• W2012108232 hasConcept C2993143319 @default.
• W2012108232 hasConcept C3013748606 @default.
• W2012108232 hasConcept C521977710 @default.
• W2012108232 hasConcept C55493867 @default.
• W2012108232 hasConcept C71240020 @default.
• W2012108232 hasConcept C86803240 @default.
• W2012108232 hasConceptScore W2012108232C142462285 @default.
• W2012108232 hasConceptScore W2012108232C159047783 @default.
• W2012108232 hasConceptScore W2012108232C178790620 @default.

• next