Department of Chemistry, Division of Chemical Biology and Medicinal Chemistry, and Department of Pharmacology, University of North Carolina, Chapel Hill, NC, 27599, USA.
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, 27599, USA.
Angew Chem Int Ed Engl. 2016 Jan 18;55(3):950-4. doi: 10.1002/anie.201508767. Epub 2015 Dec 4.
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.
尽管基于肽的治疗方法在临床上的应用越来越广泛，但通常需要进行广泛的结构修饰，以防止它们在血液中被蛋白酶迅速降解。我们已经评估了红细胞作为储库、保护盾（对抗蛋白酶）和光触发肽发射台的能力。我们设计了脂质化肽，使其锚定在红细胞表面，提供一个抗蛋白酶的环境。在脂质锚和肽骨架之间插入光可裂解部分，从而能够实现红细胞内肽的光触发释放。我们已经表明，一种细胞穿透肽、一种激素（促黑素细胞激素）和一种凝血剂可以被锚定在红细胞上，免受蛋白酶的侵害，并通过光解释放以产生所需的生物学效应。
