Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter

作者：Rashad Adel A; Sundaram Ramalingam Venkat Kalyana; Aneja Rachna; Duffy Caitlin; Chaiken Irwin^*

来源：Journal of Medicinal Chemistry, 2015, 58(18): 7603-7608.

DOI：10.1021/acs.jmedchem.5b00935

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.

• 出版日期2015-9-24