Discovery and characterization of cyclotides from Rinorea species

Document Type

Journal Article

Publication Title

Journal of Natural Products

ISSN

1520-6025

Volume

81

Issue

11

First Page

2512

Last Page

2520

PubMed ID

30387611

Publisher

ACS Publications

School

School of Science

RAS ID

28475

Comments

Niyomploy, P., Chan, L. Y., Harvey, P. J., Poth, A. G., Colgrave, M. L., & Craik, D. J. (2018). Discovery and characterization of cyclotides from Rinorea species. Journal of Natural Products.

Available here.

Abstract

Cyclotides are macrocyclic cystine-knotted peptides most commonly found in the Violaceae plant family. Although Rinorea is the second-largest genera within the Violaceae family, few studies have examined whether or not they contain cyclotides. To further our understanding of cyclotide diversity and evolution, we examined the cyclotide content of two Rinorea species found in Southeast Asia: R. virgata and R. bengalensis. Seven cyclotides were isolated from R. virgata (named Rivi1-7), and a known cyclotide (cT10) was found in R. bengalensis. Loops 2, 5, and 6 of Rivi1-4 contained sequences not previously seen in corresponding loops of known cyclotides, thereby expanding our understanding of the diversity of cyclotides. In addition, the sequence of loop 2 of Rivi3 and Rivi4 were identical to some related noncyclic "acyclotides" from the Poaceae plant family. As only acyclotides, but not cyclotides, have been reported in monocotyledons thus far, our findings support an evolutionary link between monocotyledon-derived ancestral cyclotide precursors and dicotyledon-derived cyclotides. Furthermore, Rivi2 and Rivi3 had comparable cytotoxic activities to the most cytotoxic cyclotide known to date: cycloviolacin O2 from Viola odorata; yet, unlike cycloviolacin O2, they did not show hemolytic activity. Therefore, these cyclotides represent novel scaffolds for use in future anticancer drug design.

DOI

10.1021/acs.jnatprod.8b00572

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