Natural and grafted cyclotides in cancer therapy: An insight

Journal of Peptide Science : an Official Publication of the European Peptide Society
Lovekesh MehtaSanjay Kumar

Abstract

Cyclotides is a rapidly growing class of plant-derived cyclic peptides exhibiting several bioactivities with potential applications in the agricultural and pharmaceutical sectors. Both natural and grafted cyclotides have shown promise in cancer therapy. Approximately 70 natural cyclotides belonging to three plant families (Fabaceae, Rubiaceae, and Violaceae) have shown cytotoxicity against several cancer cell lines. Cyclotides exhibit considerable stability against thermal and enzymatic proteolysis, owing to their unique structure with knotted topology and head to tail cyclization. Further, their small size, high stability, oral bioavailability, and tolerance to amino acid substitution in structural loops make them an ideal platform for designing peptide-based drugs for cancer. Thus, cyclotides provide ideal scaffolds for bioactive epitope grafting and facilitating drug delivery in cancer treatment. Many anticancer linear peptides have been grafted in cysteine knotted cyclic framework of cyclotide for enhancing their cell permeability across cellular membranes, thereby improving their delivery and pharmacokinetics. The present review comprehensively discusses the distribution, toxicity, and anticancer bioactivity of natural cyc...Continue Reading

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Citations

Apr 30, 2021·Botanical Studies·Junpeng LiXingyong Yang
Jun 23, 2021·Biochemical Society Transactions·Norelle L Daly, David T Wilson

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