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用于肿瘤免疫治疗的双特异肽的原位自组装
作者:小柯机器人 发布时间:2022/1/12 10:47:12

国家纳米科学中心Hao Wang研究小组近日取得一项新成果。经过不懈努力,他们开发了一种可以在原位自组装的用于肿瘤免疫治疗的双特异肽。相关论文于2022年1月7日发表于国际顶尖学术期刊《德国应用化学》。

精确、有效地调控蛋白质的功能仍然面临着巨大的挑战,在该文中,团队报道了一种可编程的多肽分子,它由靶向和自组装模块组成,使其特异性和高效的组装由靶向的受体蛋白控制。与细胞膜受体结合后,多肽构象随自组装活化能降低有所稳定,促进了肽-蛋白复合物的齐聚。

研究人员首先设计了一个识别整合素αVβ3受体的GNNQQNY-RGD多肽(G7-RGD),用于概念验证研究。在αVβ3蛋白的存在下,游离G7-RGD的临界组装浓度从525 μM下降到33 μM,形成的G7-RGD团簇驱动了整合素受体的齐聚。最后,研究人员合理设计了一种双特异性的组装肽——抗CD3-G7-RGD用于癌症免疫治疗,验证了CD3齐聚和伴随的T细胞活化,导致T细胞介导的癌细胞溶解。

附:英文原文

Title: In Situ Self-Assembly of Bispecific Peptide for Cancer Immunotherapy

Author: Man-Di Wang, Gan-Tian Lv, Hong-Wei An, Ni-Yuan Zhang, Hao Wang

Issue&Volume: 2022-01-07

Abstract: Precise and effective manipulation of protein functions still faces tremendous challenges. Herein we report a programmable peptide molecule, consisted of targeting and self-assembly modules, that enables specific and highly efficient assembly governed by targeting receptor proteins. Upon binding to the cell membrane receptor, peptide conformation is somewhat stabilized along with decreased self-assembly activation energy, promoting peptide-protein complex oligomerization. We first design a GNNQQNY-RGD peptide (G7-RGD) to recognize integrin α  V  β  3  receptor for proof-of-concept study. In the presence of α  V  β  3  protein, the critical assembly concentration of free G7-RGD decreases from 525 to 33 μM and the resultant G7-RGD cluster drives integrin receptor oligomerization. Finally, a bispecific assembling peptide antiCD3-G7-RGD is rationally designed for cancer immunotherapy, which validates CD3 oligomerization and concomitant T cell activation, leading to T cell-mediated cancer cell cytolysis.

DOI: 10.1002/anie.202113649

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202113649

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx