title: Peptide inhibitors of HIV-1 and HIV-2 proteases: a comparative study.
abstract: HIV-1 and HIV-2 proteases (PR) which play the key role in the formation of infectious viral particles offer a target for inhibitors that could block the maturation step. Inhibitors o HIV-1 PR exhibit mostly 1-2 orders of magnitude weaker affinity for HIV-2 PR. The subsite specificity study of the HIV-1 and HIV-2 proteases performed with inhibitors varying in the type of nonhydrolysable bonds and amino acid residues in the P1, P1'and P2'positions has led us to the design of inhibitors with 2S,4S and 2R,4S stereomeres of the hydroxyethylene isostere and Glu or Gln in the P2'positions. These compounds inhibit HIV-1 and HIV-2 proteases in vitro in subnanomolar concentrations and exhibit the activity in tissue culture.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech. Acad. Sci., Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Pichová
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: J
authors.initials: J
authors.lastname: Litera
authors.forename: J
authors.initials: J
authors.lastname: Konvalinka
authors.forename: J
authors.initials: J
authors.lastname: Vondrásek
authors.forename: M
authors.initials: M
authors.lastname: Soucek
authors.forename: P
authors.initials: P
authors.lastname: Strop
authors.forename: P
authors.initials: P
authors.lastname: Majer
authors.forename: A M
authors.initials: AM
authors.lastname: Heuser
authors.forename: H G
authors.initials: HG
authors.lastname: Kraeusslich
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D019556:COS Cells; D015195:Drug Design; D005030:Ethylenes; D015683:Gene Products, gag / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D019258:Saquinavir / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D019380:Anti-HIV Agents; D005030:Ethylenes; D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011994:Recombinant Proteins; C067254:hydroxyethylene; D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease; C065184:p16 protease, Human immunodeficiency virus 2; D019258:Saquinavir