The Plasma Membrane as a Reservoir, Protective Shield, and Light‐Triggered Launch Pad for Peptide Therapeutics. Issue 3 (4th December 2015)

• Record Type: Journal Article
• Authors: O'Banion, Colin P.; Nguyen, Luong T.; Wang, Qunzhao; Priestman, Melanie A.; Holly, Stephen P.; Parise, Leslie V.; Lawrence, David S.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 3(2016)
• Page Start: 950
• Page End: 954
• Publication Date: 2015-12-04
• Subjects: targeted delivery -- peptides -- peptide drugs -- photochemistry -- proteolysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201508767
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Although peptide‐based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light‐triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease‐resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light‐triggered peptide release from erythrocytes. We have shown that a cell‐permeable peptide, a hormone (melanocyte stimulating hormone), and a blood‐clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect. Abstract : Gimme shelter : Attachment to the plasma membrane of erythrocytes can be used to protect therapeutic peptides from serum proteases. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light‐triggered release.