Template-Tethered Collagen Mimetic Peptides for Studying Heterotrimeric Triple-Helical Interactions
Template-Tethered Collagen Mimetic Peptides for Studying Heterotrimeric Triple-Helical Interactions
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DOI：
10.1002/bip.21536
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发表时间：
2011-02-01
期刊：
影响因子：
2.9
通讯作者：
Yu, S. Michael
中科院分区：
文献类型：
--
作者：
Li, Yang;Mo, Xiao;Yu, S. Michael
胶原模拟多肽(CMPS)已被用于阐明胶原分子的三螺旋构象的结构和稳定性。虽然化学机械抛物型同源三聚体已被广泛研究，但由于合成困难，关于化学机械抛物型杂三聚体的研究报道很少。在这里，我们介绍了同源三聚体和ABB型杂三聚体的合成和表征，所述同源三聚体和ABB型杂三聚体包括共价连接到模板三(2-氨乙基)胺(Tren)琥珀酸衍生物的天然和合成的CMP序列。合成了含有CMPS[(ProHypGly)(6)，(ProProGly)(6)]和代表I型胶原特定结构域的CMPS的各种链状杂三聚体，并对其进行了三螺旋结构、热熔融行为和复性动力学的表征。结果表明，天然I型胶原衍生的CMPS能与人工合成的CMPS形成稳定的异三聚体螺旋络合物，其热稳定性和折叠速度随着肽链中螺旋稳定氨基酸(如Hyp)数目的增加而增加。共价链结提高了所有CMPS的热稳定性和折叠动力学，但它们的相对值不受影响，这表明该拴系体系可用于比较研究异三聚体CMPS的链组成和表征热不稳定CMPS的折叠行为。(C)2010 Wiley期刊，Inc.生物聚合物95：94-104,2011。
Collagen mimetic peptides (CMPs) have been used to elucidate the structure and stability of the triple helical conformation of collagen molecules. Although CMP homotrimers have been widely studied, very little work has been reported regarding CMP heterotrimers because of synthetic difficulties. Here, we present the synthesis and characterization of homotrimers and ABB type heterotrimers comprising natural and synthetic CMP sequences that are covalently tethered to a template, a tris(2-aminoethyl) amine (TREN) succinic acid derivative. Various tethered heterotrimers comprising synthetic CMPs [(ProHypGly)(6), (ProProGly)(6)] and CMPs representing specific domains of type I collagen were synthesized and characterized in terms of triple helical structure, thermal melting behavior, and refolding kinetics. The results indicated that CMPs derived from natural type I collagen sequence can form stable heterotrimeric helical complexes with artificial CMPs and that the thermal stability and the folding rate increase with the increasing number of helical stabilizing amino acids (e. g. Hyp) in the peptide chains. Covalent tethering enhanced the thermal stability and refolding kinetics of all CMPs; however, their relative values were not affected suggesting that the tethered system can be used for comparative study of heterotrimeric CMP's folding behavior in regards to chain composition and for characterization of thermally unstable CMPs. (C) 2010 Wiley Periodicals, Inc. Biopolymers 95: 94-104, 2011.