Evaluation of "norpeptides" as potential inhibitors of HIV-proteases.
Peptide mimics of substrates for HIV-proteases were prepared. These "norpeptides" are identical to a fragment of the HIV-polyprotein except that a crucial scissile bond was deleted, and an alpha,beta-disubstituted amino acid spans the P1 and P1 site. Thus all four stereoisomers of Leu psi[]Ala (i.e. H2NCH(CH2iPr)CH(Me)CO2H, 1) were incorporated into Ac-Ala-Arg-Val-Leu psi[]Ala-Glu-Ala-NH2 (all other residues being L-amino acids), and tested with respect to inhibition of HIV-1 and HIV-2 proteases.
Burgess
K
K
Department of Chemistry, Texas A&M University, College Station 77843.
Pal
B
B
D000595:Amino Acid Sequence; D004353:Drug Evaluation, Preclinical; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D015498:HIV-2 / Q000201:enzymology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D017320:HIV Protease Inhibitors; D009842:Oligopeptides