Title
Generation of a long-acting fusion inhibitor against HIV-1
Author
Ye Guo, Pan Pan Zhou, Xiao Wen Fan, Yu Wei Dou, Xuan Ling Shi
Year
2018
Journal
MedChemComm
Abstract
AIDS has evolved from a fatal infectious disease to a manageable chronic disease under the treatment of anti-AIDS medications. HIV fusion inhibitors with high activity, low side effects, strong selectivity, are promising drugs against HIV. Only one fusion inhibitor is currently approved, thereby highly active long-acting fusion inhibitors are needed to develop for long-term AIDS treament. Here, we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1-2 staples to impove it stability. Antiviral activity study showed that MT-SC22EK-2 with two staples exhibited the potent inhibitory activity agaisnt HIV-1 standard strains and Chinese epidemic strains, at the same time MT-SC22EK-2 presented the strong anti-T20 resistance. Surprisingly, MT-SC22EK-2 possessed excellent protease stability with the half-life value of 3665 min. MT-SC22EK-2 is the potential HIV fusion inhibitors to be a candidate of long-acting anti-HIV drug.
Instrument
J-715
Keywords
Circular dichroism, Secondary structure, Biochemistry