Organic & Bioorganic Chemistry Laboratory, Council of Scientific and Industrial Research (CSIR) - Central Leather Research Institute (CLRI), Adyar, Chennai 600020, India.
Centre for Academic & Research Excellence (CARE), CSIR-CLRI, Adyar, Chennai 600020, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-CLRI Campus, Chennai 600020, India.
Int J Biol Macromol. 2020 Aug 1;156:1146-1152. doi: 10.1016/j.ijbiomac.2019.11.148. Epub 2019 Nov 19.
Inhibition of collagen fibrillation by small molecules is of growing interest to develop therapeutics for the illnesses related to excess deposition of collagen. In this context, we have studied the inhibitory effect of N-Vanillylnonanamide (NVA), a natural product from capsicum oleoresin and an analog of capsaicin (a known inhibitor of collagen fibrillation), on collagen self-assembly that leads to fibrillation in vitro. Commercially, capsaicin was found to be expensive than NVA. Therefore, it would be an advantage economically if NVA could display a similar/better inhibitory activity compared to capsaicin. The conventional turbidity measurements indicate that NVA completely inhibits collagen fibrillation at body temperature (37 °C) and its inhibition were concentration-dependent. The inhibition efficiency was observed to reduce at room temperature (25 °C). NVA protects the triple helical structure of collagen while it increases the thermal stability of collagen compared to collagen alone. Fluorescence results suggest that NVA binds in both telopeptide and triple helical regions of collagen and thereby prevents collagen self-assembly. The present results thus indicate that NVA is a potential inhibitor and, economically, it could be a better choice as a therapeutic agent compared to capsaicin in evolving treatment for disorders associated with excessive collagen deposition.
小分子抑制胶原蛋白纤维形成对于开发治疗与胶原蛋白过度沉积相关疾病的疗法越来越受到关注。在这种情况下,我们研究了 N-香草基壬酰胺(NVA)对胶原蛋白自组装的抑制作用,NVA 是辣椒树脂中的一种天然产物,也是辣椒素(一种已知的胶原蛋白纤维形成抑制剂)的类似物,胶原蛋白自组装会导致体外纤维形成。从商业角度来看,辣椒素比 NVA 昂贵。因此,如果 NVA 能显示出与辣椒素相似/更好的抑制活性,从经济角度来看将是一个优势。常规的浊度测量表明,NVA 在体温(37°C)下完全抑制胶原蛋白纤维形成,其抑制作用呈浓度依赖性。在室温(25°C)下,抑制效率观察到降低。NVA 保护胶原蛋白的三螺旋结构,同时与单独的胶原蛋白相比增加了胶原蛋白的热稳定性。荧光结果表明,NVA 结合在胶原蛋白的末端肽和三螺旋区域,从而阻止胶原蛋白自组装。因此,目前的结果表明,NVA 是一种潜在的抑制剂,从经济角度来看,与辣椒素相比,它可能是治疗与胶原蛋白过度沉积相关疾病的更优选择。