Consequences of incorporating thiaproline and its oxidized derivatives into collagen triple helices
Consequences of incorporating thiaproline and its oxidized derivatives into collagen triple helices
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DOI：
10.1002/pro.4650
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发表时间：
2023-06-01
期刊：
影响因子：
8
通讯作者：
Horng, Jia-Cherng
中科院分区：
文献类型：
--
作者：
Hsu, Tsai-Ling;Horng, Jia-Cherng
（2R）-4-噻脯氨酸（Thp）是脯氨酸的类似物，用硫取代吡咯烷环上的c - γ。它的噻唑烷环由于能量势垒小，很容易在内端和外端折叠之间相互转换，从而导致脯氨酸螺旋不稳定。胶原蛋白由三个聚脯氨酸II螺旋组成，主要由X-Y- gly三联体组成，其中X常为脯氨酸，Y常为(2S,4R)-羟基脯氨酸。在这项研究中，我们将Thp纳入x位置或y位置，以研究这种置换对三螺旋结构的影响。圆二色性和差示扫描量热分析表明，含thp的模拟胶原肽（CMPs）可以折叠成稳定的三螺旋结构，其中y位置的取代表现出较大的不稳定效应。此外，我们还将肽中的Thp氧化为n -甲酰基半胱氨酸或S，S-二氧化Thp，制备了衍生肽。结果表明，x位氧化衍生物对胶原稳定性影响较小，而y位氧化衍生物对胶原稳定性影响较大。将Thp及其氧化衍生物纳入cmp的结果与位置有关。计算结果表明，Thp的外显子和内显子之间易于相互转化以及S，S-二氧化Thp的扭转构象可能导致y位置的不稳定效应。我们揭示了Thp及其氧化衍生物对胶原蛋白影响的新见解，并证明Thp可用于设计胶原相关生物材料。
(2R)-4-thiaproline (Thp) is an analog of proline, replacing C-gamma in the pyrrolidine ring with sulfur. Its thiazolidine ring easily interconverts between endo and exo puckers due to a small energy barrier, which leads to destabilize polyproline helices. Collagen, composed of three polyproline II helices, mainly consists of X-Y-Gly triplets, where X is often proline and Y is frequently (2S,4R)-hydroxyproline. In this study, we incorporated Thp into either position-X or position-Y to investigate the consequences of such a replacement on the triple helix. Circular dichroism and differential scanning calorimetry analyses showed that the Thp-containing collagen-mimetic peptides (CMPs) can fold into stable triple helices, in which the substitution at position-Y exhibits a larger destabilization effect. Additionally, we also prepared the derivative peptides by oxidizing Thp in the peptide to N-formyl-cysteine or S,S-dioxide Thp. The results showed that the oxidized derivatives at position-X only slightly affect collagen stability, but those at position-Y induce a large destabilization effect. The consequences of incorporating Thp and its oxidized derivatives into CMPs are position dependent. Computational results suggested that the ease of interconversion between exo and endo puckers for Thp and the twist conformation of S,S-dioxide Thp may cause the destabilization effect at position-Y. We have revealed new insights into the impacts of Thp and its oxidized derivatives on collagen and demonstrated that Thp can be used to design collagen-related biomaterials.