一种能够水解焦磷酸钙晶体的噬菌体展示短肽——软骨钙质沉着症的病因因子。

A Phage Display-Identified Short Peptide Capable of Hydrolyzing Calcium Pyrophosphate Crystals-The Etiological Factor of Chondrocalcinosis.

机构信息

Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.

Inter-Faculty Individual Studies in Mathematics and Natural Sciences, University of Warsaw, Stefana Banacha 2C, 02-087 Warsaw, Poland.

出版信息

Molecules. 2021 Sep 24;26(19):5777. doi: 10.3390/molecules26195777.

DOI:10.3390/molecules26195777

PMID:34641321

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8510196/

Abstract

Chondrocalcinosis is a metabolic disease caused by the presence of calcium pyrophosphate dihydrate crystals in the synovial fluid. The goal of our endeavor was to find out whether short peptides could be used as a dissolving factor for such crystals. In order to identify peptides able to dissolve crystals of calcium pyrophosphate, we screened through a random library of peptides using a phage display. The first screening was designed to select phages able to bind the acidic part of alendronic acid (pyrophosphate analog). The second was a catalytic assay in the presence of crystals. The best-performing peptides were subsequently chemically synthesized and rechecked for catalytic properties. One peptide, named R25, turned out to possess some hydrolytic activity toward crystals. Its catalysis is Mg-dependent and also works against soluble species of pyrophosphate.

摘要

软骨钙质沉着症是一种代谢性疾病，其病因是滑液中存在焦磷酸钙二水合物晶体。我们的研究目的是确定短肽是否可以用作此类晶体的溶解因子。为了鉴定能够溶解焦磷酸钙晶体的肽，我们使用噬菌体展示技术对随机肽文库进行了筛选。第一轮筛选旨在选择能够结合阿仑膦酸钠（焦磷酸盐类似物）酸性部分的噬菌体。第二轮筛选是在晶体存在的情况下进行的催化测定。表现最佳的肽随后进行了化学合成，并重新检测了其催化特性。一种名为 R25 的肽对晶体表现出一定的水解活性。其催化作用依赖于镁，并且对可溶性焦磷酸盐也有作用。