Back to Search
Start Over
A chameleonic macrocyclic peptide with drug delivery applicationsâ€
- Source :
- Chemical Science
- Publication Year :
- 2021
- Publisher :
- The Royal Society of Chemistry, 2021.
-
Abstract
- 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 β-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.<br />The cyclic peptide PDP-23 adopts a different structure depending on conditions. In water it forms a dimer, but can unfold allowing its hydrophobic core to interact with membranes. PDP-23 shows promise as a cell penetrating scaffold for drug delivery.
- Subjects :
- 0303 health sciences
biology
Chemistry
Dimer
030302 biochemistry & molecular biology
Zinnia elegans
General Chemistry
biology.organism_classification
Combinatorial chemistry
Micelle
Rhodamine
03 medical and health sciences
Macrocyclic peptide
chemistry.chemical_compound
Monomer
Drug delivery
Efflux
030304 developmental biology
Subjects
Details
- Language :
- English
- ISSN :
- 20416539 and 20416520
- Volume :
- 12
- Issue :
- 19
- Database :
- OpenAIRE
- Journal :
- Chemical Science
- Accession number :
- edsair.doi.dedup.....4cc21ac8c43d7af7356b0b51b75f46fd