Rashad Adel A, Kalyana Sundaram Ramalingam Venkat, Aneja Rachna, Duffy Caitlin, Chaiken Irwin
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.
J Med Chem. 2015 Sep 24;58(18):7603-8. doi: 10.1021/acs.jmedchem.5b00935. Epub 2015 Sep 11.
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.
我们开发了大环HIV-1拮抗剂作为一类新型的拟肽药物先导物。环肽三唑（cPTs）保留了母体三唑（PTs）的gp120抑制和病毒灭活特性，这表明环化锁定了一种活性构象。六残基cPT 9（AAR029b）在抑制细胞感染和引发导致病毒粒子不可逆失活的gp120脱落方面表现出亚微摩尔级的抗病毒效力。重要的是，与相应的线性PTs的高度敏感性相比，cPTs对胰蛋白酶和胰凝乳蛋白酶稳定。
