Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Biomacromolecules. 2020 Apr 13;21(4):1539-1547. doi: 10.1021/acs.biomac.0c00103. Epub 2020 Mar 19.
Collagen is the most abundant protein in humans and the major component of human skin. Collagen mimetic peptides (CMPs) can anneal to damaged collagen in vitro and in vivo. A duplex of CMPs was envisioned as a macromolecular mimic for damaged collagen. The duplex was synthesized on a solid support from the amino groups of a lysine residue and by using olefin metathesis to link the N termini. The resulting cyclic peptide, which is a monomer in solution, binds to CMPs to form a triple helix. Among these, CMPs that are engineered to avoid the formation of homotrimers but preorganized to adopt the conformation of a collagen strand exhibit enhanced association. Thus, this cyclic peptide enables the assessment of CMPs for utility in annealing to damaged collagen. Such CMPs have potential use in the diagnosis and treatment of fibrotic diseases and wounds.
胶原蛋白是人体内最丰富的蛋白质，也是人体皮肤的主要成分。胶原蛋白模拟肽（CMP）可以在体外和体内与受损的胶原蛋白结合。设想双股 CMP 作为受损胶原蛋白的大分子模拟物。该双股在赖氨酸残基的氨基上通过使用烯烃复分解反应连接 N 末端在固体支持物上合成。所得的环状肽在溶液中是单体，与 CMP 结合形成三螺旋。在这些 CMP 中，设计为避免形成同三聚体但预先组织以采用胶原蛋白链构象的 CMP 表现出增强的缔合。因此，这种环状肽可用于评估 CMP 对退火至受损胶原蛋白的用途。此类 CMP 在纤维化疾病和伤口的诊断和治疗中有潜在用途。
