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Development of Cell-type specific anti-HIV gp120 aptamers for siRNA delivery
Published on: June 23, 2011
Macrocyclic Envelope Glycoprotein Antagonists that Irreversibly Inactivate HIV-1 before Host Cell Encounter
Adel A Rashad1, Ramalingam Venkat Kalyana Sundaram1,2, Rachna Aneja1
1Department of Biochemistry and Molecular Biology, Drexel University College of Medicine , 245 North 15th Street, Philadelphia, Pennsylvania 19102 United States.
Abstract:
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.
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