7l54

Publication Abstract from PubMed

Head-to-tail cyclized peptides are intriguing natural products with unusual properties. The PawS-Derived Peptides (PDPs) are ribosomally synthesized as part of precursors for seed storage albumins in species of the daisy family, and are post-translationally excised and cyclized during proteolytic processing. Here we report a PDP twice the typical size and with two disulfide bonds, identified from seeds of Zinnia elegans. In water, synthetic PDP-23 forms a unique dimeric structure in which two monomers containing two beta-hairpins cross-clasp and enclose a hydrophobic core, creating a square prism. This dimer can be split by addition of micelles or organic solvent and in monomeric form PDP-23 adopts open or closed V-shapes, exposing different levels of hydrophobicity dependent on conditions. This chameleonic character is unusual for disulfide-rich peptides and engenders PDP-23 with potential for cell delivery and accessing novel targets. We demonstrate this by conjugating a rhodamine dye to PDP-23, creating a stable, cell-penetrating inhibitor of the P-glycoprotein drug efflux pump.

A chameleonic macrocyclic peptide with drug delivery applications.,Payne CD, Franke B, Fisher MF, Hajiaghaalipour F, McAleese CE, Song A, Eliasson C, Zhang J, Jayasena AS, Vadlamani G, Clark RJ, Minchin RF, Mylne JS, Rosengren KJ Chem Sci. 2021 Apr 11;12(19):6670-6683. doi: 10.1039/d1sc00692d. PMID:34040741^[1]

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