抑制人降钙素(hCT)聚集的方法

Inhibition of human calcitonin(hCT)aggregation in vitro

人降钙素(human calcitonin,h CT)是一种由甲状腺滤泡旁细胞合成和分泌的含32个氨基酸残基的肽类激素,参与体内骨质代谢的调节,临床可用于治疗骨代谢相关疾病。然而,hCT的易聚集特性导致其生物活性降低,并产生毒副作用,使其临床应用受到限制。因此,目前临床上使用不易聚集的鲑鱼降钙素(salmon calcitonin,sCT)替代。由于sCT与hCT只有50%的氨基酸序列同源性,异源所致的继发耐药性是sCT长期治疗中的一个重要问题。基于此,许多研究又将焦点集中到如何抑制hCT聚集方面,希望通过有效手段阻止hCT聚集,将其重新应用于临床。本文综述了近年来抑制hCT聚集的研究进展,为其临床替代sCT提供参考。

Human calcitonin(hCT)is a 32-residue hormone synthesized and secreted by the parafollicular cells of the thyroid and plays an important role in skeletal protection and calcium regulation.Despite some success as a therapeutic agent for bone-related diseases,hCT’s ability to control these diseases is limited by its extremely high tendency to aggregate along the canonical amyloid aggregation pathway,compromising its therapeutic efficacy and safety.Therefore,h CT aggregation constitutes a serious problem that leads to a significant decrease in the hormone activity.At present,salmon calcitonin(sCT)is widely used to replace hCT.This is because s CT shows a substantially lower propensity to aggregate.However,since sCT has only 50%sequence homology with hCT,the drug resistance caused by heterologous is a big problem in the long-term treatment of sCT,and h CT would not produce such immune response.Furthermore,it is reported that when aggregation is prevented by drastic chemical conditions,hCT shows a much higher physiological activity than sCT.Based on this,many studies focus on how to inhibit h CT aggregation,hoping to prevent hCT aggregation by effective means and rescue it to clinical practice.In order to understand the achievements of inhibiting hCT aggregation in recent years,we classified the inhibitory methods into two categories:one is through modification or mutation of h CT,the other is to add inhibitors.In this paper,we reviewed both ways to lay a foundation for its clinical replacement of sCT.