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Molecular Basis of Human Defensins as Novel Lipid II Binding Peptide Antibiotics

人类防御素作为新型脂质 II 结合肽抗生素的分子基础

基本信息

批准号：
8320100
负责人：
Erik de Leeuw
金额：
$ 19.19万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-15 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8320100
关键词：
Acute Anabolism Anti-Bacterial Agents Anti-Infective Agents Antibiotic Resistance Antibiotics Bacteria Bacterial Infections Binding Biochemical Biological Assay Cell Wall Charge Clinical Defensins Development Disulfides Electrostatics Family Frequencies Goals Gram-Positive Bacteria Host Defense Human Infection Knowledge Lead Light Lipid Binding Lipids Membrane Molecular Multi-Drug Resistance Mutate Mutation Natural Immunity Outcome Patients Peptide Antibiotics Peptides Pharmaceutical Preparations Prevalence Prevention Reporting Research Resistance Therapeutic Time Validation Virus Diseases analog antimicrobial antimicrobial drug antimicrobial peptide bacterial resistance base combat disulfide bond fighting human neutrophil peptide 1 infectious disease treatment innovation insight killings man membrane biogenesis microbial novel pathogen research study

项目摘要

DESCRIPTION (provided by applicant): The prevalence of resistant bacterial pathogens is rendering current antibiotics ineffective, and making it essential that new drugs be developed to fight infection. Defensins are antimicrobial peptides that protect man against bacterial and viral infections and have a wide range as potential anti-infective therapeutics. This proposal identifies Lipid II, an essential precursor in bacterial membrane biogenesis, as a potential target of defensin antibacterial activity for the first time. The overall objective of our study is to define functional and structural interactions between defensins and Lipid II. In the long term, we aim to apply the knowledge gained in our research towards the development of defensin-based antibiotic compounds targeting Lipid II to combat Gram-positive pathogenic infections.

描述（由申请人提供）：耐药细菌病原体的流行使目前的抗生素无效，因此必须开发新药来对抗感染。防御素是一种具有抗细菌和病毒感染作用的抗菌肽，具有广泛的抗感染活性。该提案首次将细菌膜生物合成中的重要前体脂质II确定为防御素抗菌活性的潜在靶点。我们研究的总体目标是确定防御素和脂质II之间的功能和结构相互作用。从长远来看，我们的目标是将我们研究中获得的知识应用于开发基于防御素的抗生素化合物，以脂质II为靶点，以对抗革兰氏阳性病原体感染。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（4）

Structure-activity exploration of a small-molecule Lipid II inhibitor.

DOI：
10.2147/dddt.s79504
发表时间：
2015
期刊：
Drug design, development and therapy
影响因子：
0
作者：
Fletcher S;Yu W;Huang J;Kwasny SM;Chauhan J;Opperman TJ;MacKerell AD Jr;de Leeuw E
通讯作者：
de Leeuw E

Turning defense into offense: defensin mimetics as novel antibiotics targeting lipid II.

DOI：
10.1371/journal.ppat.1003732
发表时间：
2013
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Varney KM;Bonvin AM;Pazgier M;Malin J;Yu W;Ateh E;Oashi T;Lu W;Huang J;Diepeveen-de Buin M;Bryant J;Breukink E;Mackerell AD Jr;de Leeuw EP
通讯作者：
de Leeuw EP

Effect of a small molecule Lipid II binder on bacterial cell wall stress.

小分子脂质 II 结合剂对细菌细胞壁应激的影响。