Inhibition of HIV-1 protease by short peptides derived from the terminal segments of the protease.
The active HIV-1 protease is a homodimeric enzyme. A beta-sheet consisting of N- and C-terminal segments provides the main driving force for dimerization of the inactive protomers. Several short peptides with sequences derived from the N- and C-termini of the protease were tested for inhibition of protease activity and for inhibition of HIV-1 replication in lymphocytes. Medium inhibitory activity was found with each of the peptides in the enzyme test and no inhibition of the lymphocytes was found up to 200 micrograms/ml. The enzyme tests indicate that HIV-1 protease is the target of the inhibitory action. Synergistic action could not be found with pairs of the peptides derived from the two different termini. Prolonged incubation with one of the peptides increased inhibition indicating a slow dissociation of the protease dimers. No cytotoxic effect of the inhibitors could be found below 200 micrograms/ml.
Schramm
H J
HJ
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Breipohl
G
G
Hansen
J
J
Henke
S
S
Jaeger
E
E
Meichsner
C
C
Riess
G
G
Ruppert
D
D
Rücknagel
K P
KP
Schäfer
W
W
D000595:Amino Acid Sequence; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002478:Cells, Cultured; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000201:enzymology* / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007700:Kinetics; D008214:Lymphocytes; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D007376:Interleukin-2; D009842:Oligopeptides; D011994:Recombinant Proteins; D016333:HIV Protease