The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics
| Autor: | David S. Lawrence, Qunzhao Wang, Colin P. O'Banion, Melanie A. Priestman, Luong T. Nguyen, Stephen P. Holly, Leslie V. Parise |
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| Rok vydání: | 2015 |
| Předmět: |
Proteases
Melanocyte-stimulating hormone Proteolysis Peptide 010402 general chemistry 01 natural sciences Catalysis Cell membrane medicine Humans Amino Acid Sequence Peptide sequence chemistry.chemical_classification medicine.diagnostic_test 010405 organic chemistry Cell Membrane HEK 293 cells Membrane Proteins General Medicine General Chemistry Combinatorial chemistry 0104 chemical sciences Cell biology HEK293 Cells medicine.anatomical_structure Membrane protein chemistry Peptides HeLa Cells |
| Zdroj: | Angewandte Chemie International Edition. 55:950-954 |
| ISSN: | 1433-7851 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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