设计和合成 MDA-9/Syntenin 的小分子探针。

IF 4.8 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biomolecules Pub Date : 2024-10-12 DOI:10.3390/biom14101287

Nehru Viji Sankaranarayanan, Bharath Kumar Villuri, Balaji Nagarajan, Sarah Lewicki, Swadesh K Das, Paul B Fisher, Umesh R Desai

{"title":"设计和合成 MDA-9/Syntenin 的小分子探针。","authors":"Nehru Viji Sankaranarayanan, Bharath Kumar Villuri, Balaji Nagarajan, Sarah Lewicki, Swadesh K Das, Paul B Fisher, Umesh R Desai","doi":"10.3390/biom14101287","DOIUrl":null,"url":null,"abstract":"MDA-9/Syntenin, a key scaffolding protein and a molecular hub involved in a diverse range of cell signaling responses, has proved to be a challenging target for the design and discovery of small molecule probes. In this paper, we report on the design and synthesis of small molecule ligands of this key protein. Genetic algorithm-based computational design and the five-eight step synthesis of three molecules led to ligands with affinities in the range of 1-3 µM, a 20-60-fold improvement over literature reports. The design and synthesis strategies, coupled with the structure-dependent gain or loss in affinity, afford the deduction of principles that should guide the design of advanced probes of MDA-9/Syntenin.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505911/pdf/","citationCount":"0","resultStr":"{\"title\":\"Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin.\",\"authors\":\"Nehru Viji Sankaranarayanan, Bharath Kumar Villuri, Balaji Nagarajan, Sarah Lewicki, Swadesh K Das, Paul B Fisher, Umesh R Desai\",\"doi\":\"10.3390/biom14101287\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"MDA-9/Syntenin, a key scaffolding protein and a molecular hub involved in a diverse range of cell signaling responses, has proved to be a challenging target for the design and discovery of small molecule probes. In this paper, we report on the design and synthesis of small molecule ligands of this key protein. Genetic algorithm-based computational design and the five-eight step synthesis of three molecules led to ligands with affinities in the range of 1-3 µM, a 20-60-fold improvement over literature reports. The design and synthesis strategies, coupled with the structure-dependent gain or loss in affinity, afford the deduction of principles that should guide the design of advanced probes of MDA-9/Syntenin.\",\"PeriodicalId\":8943,\"journal\":{\"name\":\"Biomolecules\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505911/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomolecules\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/biom14101287\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomolecules","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/biom14101287","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

MDA-9/Syntenin是一种关键的支架蛋白，也是参与多种细胞信号反应的分子枢纽，已被证明是设计和发现小分子探针的一个具有挑战性的靶点。本文报告了这一关键蛋白的小分子配体的设计与合成。通过基于遗传算法的计算设计和三个分子的五步合成，我们得到了亲和力在 1-3 µM 之间的配体，比文献报道提高了 20-60 倍。这些设计和合成策略以及亲和力的增减与结构有关，为设计 MDA-9/Syntenin 的高级探针提供了指导原则。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Design and Synthesis of Small Molecule Probes of MDA-9/Syntenin.

MDA-9/Syntenin, a key scaffolding protein and a molecular hub involved in a diverse range of cell signaling responses, has proved to be a challenging target for the design and discovery of small molecule probes. In this paper, we report on the design and synthesis of small molecule ligands of this key protein. Genetic algorithm-based computational design and the five-eight step synthesis of three molecules led to ligands with affinities in the range of 1-3 µM, a 20-60-fold improvement over literature reports. The design and synthesis strategies, coupled with the structure-dependent gain or loss in affinity, afford the deduction of principles that should guide the design of advanced probes of MDA-9/Syntenin.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Biomolecules Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.40

自引率

3.60%

发文量

1640

审稿时长

18.28 days

期刊介绍： Biomolecules (ISSN 2218-273X) is an international, peer-reviewed open access journal focusing on biogenic substances and their biological functions, structures, interactions with other molecules, and their microenvironment as well as biological systems. Biomolecules publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.