Huang Pei-Wen, Chang Juyn-Ming, Horng Jia-Cherng
Department of Chemistry, National Tsing Hua University, 101 Sec. 2 Kuang-Fu Rd., Hsinchu, 30013, Taiwan, ROC.
Frontier Research Center on Fundamental and Applied Science of Matters, National Tsing Hua University, 101 Sec. 2 Kuang-Fu Rd., Hsinchu, 30013, Taiwan, ROC.
Amino Acids. 2016 Dec;48(12):2765-2772. doi: 10.1007/s00726-016-2312-2. Epub 2016 Aug 13.
Functionalized collagen-mimetic peptides (CMPs) have been widely used in the preparation of collagen-related biomaterials. Among the reported results, the induced noncovalent interactions between the implanted functional groups or moieties were frequently the key elements to promote the self-assembly of small CMPs. In this work, we designed and synthesized a series of glycosylated CMPs in which 4-O-[β-D-galactopyranosyl]-(2S,4R)-4-hydroxyproline (Hyp(Gal)) was incorporated to explore the effects of glycosylation on the stability and assembly of collagen triple helices. Circular dichroism measurements showed that glycosylation of hydroxyproline slightly destabilized the collagen triple helices, but did not reduce their refolding rate. Compared to non-glycosylated CMPs, the incorporation of Hyp(Gal) speeded up the assembly of CMPs, indicating that this modification could assist the self-assembly of CMPs into higher-order structures, such as fibrils. O-Galactosylation of hydroxyproline imposes contrary effects on the triple helix stability and the self-assembly rate of collagen triple helices, exhibiting a piece of important and useful information for designing collagen-related biomaterials. Our finding also suggests that instead of stabilizing the triple helical conformation of CMPs, installing additional forces between CMPs could be a crucial factor to promote the assembly of CMPs into large-scale constructs.
功能化的胶原模拟肽（CMPs）已被广泛用于制备与胶原相关的生物材料。在已报道的结果中，植入的官能团或部分之间诱导的非共价相互作用常常是促进小CMPs自组装的关键因素。在这项工作中，我们设计并合成了一系列糖基化的CMPs，其中引入了4-O-[β-D-吡喃半乳糖基]-(2S,4R)-4-羟基脯氨酸（Hyp(Gal)），以探索糖基化对胶原三螺旋稳定性和组装的影响。圆二色性测量表明，羟脯氨酸的糖基化略微破坏了胶原三螺旋的稳定性，但并未降低其重折叠速率。与非糖基化的CMPs相比，Hyp(Gal)的引入加速了CMPs的组装，表明这种修饰可以帮助CMPs自组装成更高阶的结构，如纤维。羟脯氨酸的O-半乳糖基化对胶原三螺旋的稳定性和自组装速率产生相反的影响，为设计与胶原相关的生物材料提供了一条重要且有用的信息。我们的发现还表明，促进CMPs组装成大规模结构的关键因素可能不是稳定CMPs的三螺旋构象，而是在CMPs之间引入额外的作用力。
