title: The nontoxic tripeptide glycyl-prolyl-glycine amide inhibits the replication of human immunodeficiency virus type 1.
abstract: OBJECTIVE
  To determine whether short peptides corresponding to the RGPGR motif of the V3 loop of gp 120 have anti-human immunodeficiency virus type 1 (anti-HIV-1) activity.
  
  
  METHODS
  Short peptides were tested against the HIV-1 laboratory strains and clinical isolates.
  
  
  RESULTS
  The tripeptide glycyl-prolyl-glycine amide (GPG-NH2) inhibited the replication of both laboratory strains and 47 clinical isolates, including 19 strains that were resistant to other drugs or that were from patients with failing therapy. The 50% inhibitory concentrations values were 2.7 to 37 microM. Phenotypic change of two isolates from nonsyncytia-inducing to syncytia-inducing did not change their sensitivity to GPG-NH2. The tripeptide added to the antiviral effect of both zidovudine and ritonavir.
  
  
  CONCLUSIONS
  The tripeptide GPG-NH2 is a nontoxic compound that inhibits the replication of HIV-1 by an apparently new mode of action. Glycyl-prolyl-glycine-NH2 might prove useful by itself or as a lead compound for the treatment of drug-resistant HIV-1. Glycyl-prolyl-glycine-NH2 is currently undergoing phase I/II human clinical trials in Sweden.
authors.affiliation: Division of Clinical Virology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Su
authors.forename: E
authors.initials: E
authors.lastname: Andersson
authors.forename: P
authors.initials: P
authors.lastname: Horal
authors.forename: M H
authors.initials: MH
authors.lastname: Naghavi
authors.forename: A
authors.initials: A
authors.lastname: Palm
authors.forename: Y P
authors.initials: YP
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Eriksson
authors.forename: M
authors.initials: M
authors.lastname: Jansson
authors.forename: H
authors.initials: H
authors.lastname: Wigzell
authors.forename: B
authors.initials: B
authors.lastname: Svennerholm
authors.forename: A
authors.initials: A
authors.lastname: Vahlne
mesh_terms: D000577:Amides / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D004357:Drug Synergism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D015394:Molecular Structure; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*; D015215:Zidovudine / Q000494:pharmacology
chemical_list: D000577:Amides; D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D017320:HIV Protease Inhibitors; C059762:HIV envelope protein gp120 (305-321); D009842:Oligopeptides; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; C425285:glycylprolylglycine amide; D019438:Ritonavir