Naturally Occurring Cyclic Peptides and Their Potential Application in HIV Therapeutics
2012
Gerlach, Samantha L. | Mondal, Debasis
AIDS is a global pandemic. Despite the success of HAART, many HIV drugs exhibit suboptimal therapeutics due to low absorption and rapid drug efflux. These attributes allow uninhibited viral propagation, promote drug resistance, and increase the dosage required to achieve efficacy. Considerable efforts to increase drug bioavailability by developing efflux inhibitors have had limited success; thus, new strategies to improve cellular drug uptake are vital. Linear peptides play important roles in immune response, but their free N and C termini represent target points of attack by enzymes; therefore, the evolutionary advantages of cyclic proteins include reduced sensitivity to enzymes and enhanced structural stability. Cyclic peptides are commonly involved in host defense and some are exceptionally stable; features that increase their appeal in biomedical research. Cyclotides, plant-derived circular peptides, exhibit a range of bioactivities that may be regulated by membrane interactions, specifically via pore formation at the lipid bilayer. Several cyclotides display anti-HIV activity, and preliminary studies indicate they can chemosensitize drug resistant cells and increase the uptake of HIV-1 agents. Therefore, this review focuses on the discovery, structure-activity relationships, and potential application of naturally occurring cyclic peptides in the treatment of HIV.
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