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Synthesis of novel brevicidine and laterocidine analogues active against multi-drug-resistant Gram-negative bacteria

对多重耐药革兰氏阴性菌具有活性的新型 brevicidine 和ateterocidine 类似物的合成

基本信息

批准号：
EP/T01783X/1
负责人：
Stephen Cochrane
金额：
$ 49.87万
依托单位：
Queen's University Belfast
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FT01783X%2F1
关键词：
Synthesis novel brevicidine laterocidine analogues

项目摘要

Combatting antimicrobial resistance is one of the most significant challenges facing our generation. Bacteria are relentlessly developing new resistance mechanisms against clinical antibiotics, making infections much harder to treat. Therefore, there is an urgent need for new antimicrobial compounds and targets. Brevicidine and laterocidine are antimicrobial peptides that have strong activity against multidrug-resistant Gram-negative bacteria, a class of bacteria that are much harder to kill as they have an extra cell membrane. They are even active against Gram-negative organisms resistant to colistin, our current antibiotic of last resort. Therefore these peptides could be excellent antibiotic candidates. However, they are difficult to prepare by chemical synthesis and less stable than other types of cyclic peptides, and the mechanism by which they kill bacteria is not known. This project aims to develop new brevicidine and laterocidine analogues that are more stable, easier to prepare and have enhanced antimicrobial activity. We will also determine how they kill bacteria, which is important knowledge if these peptides are to become antibiotics.

对抗抗生素耐药性是我们这一代面临的最重大挑战之一。细菌对临床抗生素不断产生新的耐药机制，使感染更难治疗。因此，迫切需要新的抗菌化合物和靶标。Brevicidine和laterocidine是抗微生物肽，对多重耐药革兰氏阴性菌具有很强的活性，这是一类由于具有额外细胞膜而难以杀死的细菌。它们甚至对革兰氏阴性微生物具有活性，这些微生物对粘菌素（我们目前的最后抗生素）具有抗性。因此，这些肽可能是优良的抗生素候选物。然而，它们很难通过化学合成制备，并且比其他类型的环肽更不稳定，并且它们杀死细菌的机制尚不清楚。该项目旨在开发更稳定、更容易制备并具有增强的抗菌活性的新的短杀菌素和laterocidine类似物。我们还将确定它们如何杀死细菌，如果这些肽要成为抗生素，这是重要的知识。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Targeting membrane-bound bacterial cell wall precursors: a tried and true antibiotic strategy in nature and the clinic.

靶向膜结合细菌细胞壁前体：自然界和临床中经过验证的真实抗生素策略。

DOI：
10.1039/d3cc01070h
发表时间：
2023
期刊：
Chemical communications (Cambridge, England)
影响因子：
0
作者：
Buijs NP
通讯作者：
Buijs NP

Synthetic Studies with the Brevicidine and Laterocidine Lipopeptide Antibiotics Including Analogues with Enhanced Properties and in vivo Efficacy

Brevicidine 和 Laterocidine 脂肽抗生素（包括具有增强特性和体内功效的类似物）的合成研究

DOI：
10.26434/chemrxiv-2022-15r0h-v2
发表时间：
2022
期刊：
影响因子：
0
作者：
Al-Ayed K
通讯作者：
Al-Ayed K

Linearization of the Brevicidine and Laterocidine Lipopeptides Yields Analogues That Retain Full Antibacterial Activity.

DOI：
10.1021/acs.jmedchem.3c00308
发表时间：
2023-04-27
期刊：
JOURNAL OF MEDICINAL CHEMISTRY
影响因子：
7.3
作者：
Ballantine, Ross D.;Al Ayed, Karol;Bann, Samantha J.;Hoekstra, Michael;Martin, Nathaniel I.;Cochrane, Stephen A.
通讯作者：
Cochrane, Stephen A.

The tridecaptins: non-ribosomal peptides that selectively target Gram-negative bacteria.

Tridecaptins：选择性靶向革兰氏阴性细菌的非核糖体肽。