用于分离蛇毒整合素拮抗剂的基于细胞的黏附测定法

Cell-Based Adhesion Assays for Isolation of Snake Venom's Integrin Antagonists.

作者信息

Lazarovici Philip, Marcinkiewicz Cezary, Lelkes Peter I

机构信息

Faculty of Medicine, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.

Department of Bioengineering, College of Engineering, Temple University, Philadelphia, PA, USA.

出版信息

Methods Mol Biol. 2020;2068:205-223. doi: 10.1007/978-1-4939-9845-6_11.

DOI:10.1007/978-1-4939-9845-6_11

PMID:31576530

Abstract

Snake venoms could lead to the development of new drugs to treat a range of life-threatening conditions like cardiovascular diseases. Most snake venoms contain a large variety of lethal toxins as well as anti-adhesive proteins such as disintegrins, which have evolved from the harmless compounds ADAMs (proteins with a disintegrin and a metalloprotease domain) and C-type lectin proteins which disturb connective tissue and cell-matrix interaction. These anti-adhesive proteins target and block integrin receptors and disrupt normal biological processes in snakes' prey such as connective tissue physiology and blood clotting. This chapter provides the experimental details of a practical, cell-based adhesion protocol to help identify and isolate disintegrins and C-type lectin proteins from snake venoms, important tools in integrin research and lead compounds for drug discovery.

摘要

蛇毒可能会促使开发出用于治疗一系列危及生命的疾病（如心血管疾病）的新药。大多数蛇毒含有多种致命毒素以及抗黏附蛋白，如去整合素，它们是从无害化合物ADAMs（具有去整合素和金属蛋白酶结构域的蛋白质）和C型凝集素蛋白进化而来的，这些蛋白会干扰结缔组织和细胞-基质相互作用。这些抗黏附蛋白靶向并阻断整合素受体，扰乱蛇类猎物的正常生物过程，如结缔组织生理学和血液凝固。本章提供了一个基于细胞的实用黏附实验方案的详细实验细节，以帮助从蛇毒中鉴定和分离去整合素和C型凝集素蛋白，这些是整合素研究中的重要工具和药物发现的先导化合物。