5xiv

Publication Abstract from PubMed

Hyperdisulfide-constrained peptides are distinguished by their high stability and diverse functions. Thus far, these peptides have been reported from animals only but their occurrence in plants are rare. Here, we report the discovery, synthesis and characterization of a hyperdisulfide-constrained peptides family of approximately 2 kDa, beta-ginkgotides (beta-gB1 and beta-gB2) from Ginkgo biloba. Proteomic analysis showed beta-ginkgotides contain 1820 amino acids, of which 16 residues form a conserved six-cysteine core with a highly clustered cysteine spacing of CCCCCC, an arrangement that has not been reported in cysteine-rich peptides. Disulfide mapping revealed a novel disulfide connectivity of CysIIV, CysIIVI and CysIIIV. Oxidative folding of synthetic beta-gB1 to the native form was obtained in 70% yield. The synthetic beta-gB1 displays a compact structure with no regular secondary structural elements, as determined by NMR spectroscopy. Transcriptomic analysis showed precursor betagb1 has a four-domain architecture and revealed an additional 76 beta-ginkgotide-like peptides in 59 different gymnosperms, but none in angiosperms. Phylogenetic clustering analysis demonstrated beta-ginkgotides belong to a new cysteine-rich peptide family. beta-Ginkgotide is resistant to thermal, chemical and proteolytic degradation. Together, beta-ginkgotides represent the first-in-class hyperdisulfide-constrained peptide family from plants with a novel scaffold that could be useful for engineering metabolically stable peptidyl therapeutics.

beta-Ginkgotides: Hyperdisulfide-constrained peptides from Ginkgo biloba.,Wong KH, Tan WL, Xiao T, Tam JP Sci Rep. 2017 Jul 21;7(1):6140. doi: 10.1038/s41598-017-06598-x. PMID:28733600^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.