Collagen structure in biological tissues imparts its intrinsic physical properties by the formation of several covalent crosslinks. For the first time, two major crosslinks in the skin dihydroxylysinonorleucine (HLNL) and histidinohydroxymerodesmosine (HHMD), were isotopically labelled and then analysed by liquid-chromatography high-resolution accurate-mass mass spectrometry (LC-HRMS) and small-angle neutron scattering (SANS). The isotopic labelling followed by LC-HRMS confirmed the presence of one imino group in both HLNL and HHMD, making them more susceptible to degrade at low pH. The structural changes in collagen due to extreme changes in the pH and chrome tanning were highlighted by the SANS contrast variation between isotopic labelled and unlabelled crosslinks. This provided a better understanding of the interaction of natural crosslinks with the chromium sulphate in collagen suggesting that the development of a benign crosslinking method can help retain the intrinsic physical properties of the leather. This analytical method can also be applied to study artificial crosslinking in other collagenous tissues for biomedical applications.

中文翻译：

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使用LC-HRMS和SANS对I型皮肤胶原蛋白中同位素标记的天然交联进行定量和结构分析

生物组织中的胶原蛋白结构通过形成一些共价交联键而赋予其固有的物理特性。同位素标记皮肤中的二羟基赖氨酸正亮氨酸（HLNL）和组氨酸羟基蛋氨酸（HHMD）的两个主要交联，然后通过液相色谱高分辨率精确质量质谱（LC-HRMS）和小角度中子散射进行首次分析（SANS）。同位素标记和LC-HRMS证实了HLNL和HHMD中均存在一个亚氨基，从而使其在低pH下更易降解。同位素标记和未标记交联之间的SANS对比变化突显了由于pH和鞣革的极端变化而导致的胶原蛋白结构变化。这提供了对天然交联剂与胶原蛋白中硫酸铬相互作用的更好理解，表明良性交联方法的发展可以帮助保留皮革的固有物理性能。该分析方法还可用于研究其他胶原组织中的人工交联，以用于生物医学应用。