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The Plasma Membrane as a Reservoir, Protective Shield, and Light‐Triggered Launch Pad for Peptide Therapeutics
Author(s) -
O'Banion Colin P.,
Nguyen Luong T.,
Wang Qunzhao,
Priestman Melanie A.,
Holly Stephen P.,
Parise Leslie V.,
Lawrence David S.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201508767
Subject(s) - proteases , peptide , protease , chemistry , biophysics , membrane , microbiology and biotechnology , biochemistry , enzyme , biology
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.