Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.2.1.1 (ACS)
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The conformational rearrangement of N- and C-heptad repeats (NHR, CHR) of the HIV-1 glycoprotein-41 (gp41) ectodomain into a trimer of hairpins triggers virus-cell fusion by bringing together membrane-spanning N- and C-terminal domains. Peptides derived from the NHR and CHR inhibit fusion by targeting a prehairpin intermediate state of gp41. Typically, peptides derived from the CHR are low nanomolar inhibitors, whereas peptides derived from the NHR are low micromolar inhibitors. Here, we describe the inhibitory activity of swapped-domain gp41 mimics of the form CHR-loop-NHR, which were designed to form reverse hairpin trimers exposing NHR grooves. We observed low nanomolar inhibition of HIV fusion in constructs that possessed the following properties: an extended NHR C-terminus, an exposed conserved hydrophobic pocket on the NHR, high helical content, and trimer stability. Low nanomolar activity was independent of CHR length. CD studies in membrane mimetic dodecylphosphocholine micelles suggested that bioactivity could be related to the ability of the inhibitors to interact with a membrane-associated prehairpin intermediate. The swapped-domain design resolves the problem of unstable and weakly active NHR peptides and suggests a different mechanism of action from that of CHR peptides in inhibition of HIV-1 fusion.
ACS Chem Biol 2015 May 15
PMID:Swapped-domain constructs of the glycoprotein-41 ectodomain are potent inhibitors of HIV infection. 2564 44

Cis,syndiotacticA-alt-B copolymers, where A and B are two enantiomerically pure trans-2,3-disubstituted-5,6-norbornenes with "opposite" chiralities, can be prepared with stereogenic-at-metal initiators of the type M(NR)(CHR')(OR")(pyrrolide). Formation of a high percentage of alternating AB copolymer linkages relies on an inversion of chirality at the metal with each propagating step and a relatively fast formation of an AB sequence as a consequence of a preferred diastereomeric relationship between the chirality at the metal and the chirality of the monomer. This approach to formation of an alternating AB copolymer contrasts dramatically with the principle of forming AB copolymers from achiral monomers and catalysts.
ACS Cent Sci 2016 Sep 28
PMID:Synthesis of Cis,syndiotactic A-alt-B Copolymers from Two Enantiomerically Pure Trans-2,3-Disubstituted-5,6-Norbornenes. 2772 61