| Summary: | Cyclotides are plant-derived, cyclic miniproteins with three interlocking
disulfide bonds that have attracted great interests from researchers
because of their potential as candidates for novel peptide therapeutics.
Cyclotides are highly resistant against thermal, chemical and enzymatic
degradation. In this project, we investigate the biological activities and
pharmacokinetics of cliotides, which are cyclotides from the butterfly pea
Clitoria ternatea, a well-known traditional Indian Ayurverdic herbal
medicine with various therapeutic benefits. Cliotides display potent
antibacterial activity specifically towards Gram-negative bacteria with
minimal inhibitory concentrations of as low as 0.5 IJM. They are cytotoxic
against cancer cells with ICso values at low IJM range. Remarkably,
cliotides display prominent immunomodulatory activity by enhancing the
secretion of cytokines and chemokines at concentration as low as 40 nM
in human monocytes in both resting and LPS-stimulated states. We also
develop an analytical platform using quantitative proteomic techniques to
study pharmacokinetic behavior of cliotides in rats. We show that cliotides
have relatively long elimination half-life of 2-20 hr, as compared to a few
minutes for conventional peptide and protein drugs; and their kinetics
follows the two-compartment model. These findings suggest cliotides
constitute one of the active principles in C. ternatea and hence serve as
potential candidates for novel therapeutics development.
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