The tripeptide glycyl-prolyl-glycine amide does not affect the early stepsof the human immunodeficiency virus type 1 replication

Objective: To determine whether the peptide glycyl-prolylglycine amide (GPG -NH2) corresponding to a conserved motif in the tip of the third hypervaria ble region of gp120 affected the early events in the human immunodeficiency virus type 1(HIV-1) replication. Design/Methods: Glycl-prolyl-glycine amide was tested for its effect on HIV -1 adsorption, to-receptor usage, proviral DNA synthesis, messenger RNA (mR NA) synthesis and splicing, translation, tat/TAR transactivation, and virus protease activity. Results: Glycyl-prolyl-glycine amide did not appear to affect the early eve nts of the virus replication. HIV-1 having glycine-leucine-glycine cine ins tead of GPG in the V3 loop and the mutants deleted of the GPG motif were st ill inhibited by the peptide. Glycyl-prolyl-glycine-NH2 had no discernible effect on any of the other steps in the virus replication cycle tested. The only effect observed was an increased sodium dodecyl sulfate polyacrylamid e amide gel electrophoresis mobility of gp160/120 at high concentrations of GPG-NH2. Conclusions: The tripeptide GPG-NH2 is a nontoxic compound that inhibits th e replication of HIV-1 by an apparently new mode of action.