Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter.
We derived macrocyclic HIV-1 antagonists as a new class of peptidomimetic drug leads. Cyclic peptide triazoles (cPTs) retained the gp120 inhibitory and virus-inactivating signature of parent PTs, arguing that cyclization locked an active conformation. The six-residue cPT 9 (AAR029b) exhibited submicromolar antiviral potencies in inhibiting cell infection and triggering gp120 shedding that causes irreversible virion inactivation. Importantly, cPTs were stable to trypsin and chymotrypsin compared to substantial susceptibility of corresponding linear PTs.
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.
Adel A
AA
Rashad
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.|School of Biomedical Engineering, Science and Health Systems, Drexel University , Philadelphia, Pennsylvania 19104 United States.
Ramalingam Venkat
RV
Kalyana Sundaram
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.
Rachna
R
Aneja
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.
Caitlin
C
Duffy
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.
Irwin
I
Chaiken
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D002918:Chymotrypsin / Q000737:chemistry; D015699:HIV Envelope Protein gp120 / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014357:Trypsin / Q000737:chemistry; D014771:Virion / Q000187:drug effects / Q000502:physiology; D053586:Virus Internalization
D019380:Anti-HIV Agents; D015699:HIV Envelope Protein gp120; D009842:Oligopeptides; D010456:Peptides, Cyclic; D014230:Triazoles; D002918:Chymotrypsin; D014357:Trypsin