Development of Novel Antimicrobial Peptide Mimics

新型抗菌肽模拟物的开发

基本信息

  • 批准号:
    8134342
  • 负责人:
  • 金额:
    $ 146.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-09 至 2014-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Ceragenins are small molecule mimics of endogenous antimicrobial peptides. They are broad-spectrum antimicrobial agents with activity against common and drug-resistant pathogens. Antimicrobial peptides play a central role in controlling bacterial growth in multiple tissues, including in the gastrointestinal tract. Antimicrobial peptides have been found in organisms ranging from humans to insects, and their ubiquity argues that they have evolved independently numerous times. This observation argues that the mechanism by which they eliminate bacteria provides a sustainable means of controlling bacterial growth. However, antimicrobial peptides are relatively difficult to prepare on a large scale and in general they are substrates for proteases. The ceragenins are relatively simple to prepare, and because they are not based on peptides, they are not substrates for proteases. In multiple direct comparisons of ceragenins and selected antimicrobial peptides, their mechanisms of action are indistinguishable. Intestinal infections kill millions of people annually, hinder the development of tens of millions of children, prolong hospital stays, increase mortality of hospitalized patients, and have become a concern as potential means of bioterrorism by contamination of water and food. The emergence of drug-resistant pathogens causing intestinal infections has added to this concern and has contributed to the call for new antimicrobials that will not engender resistance. The ceragenins are active against intestinal pathogens and are well- tolerated orally. Steps toward clinical use of the ceragenins include large-scale synthesis, formulation, toxicity and effacy studies. These steps are proposed. In addition, specific ceragenins display very high levels of activity against certain clinical isolates of Clostridium difficile, and it is expected that minor modifications to ceragenins will result in compound with broad, selective activity against this human pathogen. Studies of the interactions with membranes from C. difficile and a modest structure-activity study are proposed to better target ceragenins to C. difficile. RELEVANCE (See instructions): Targeted organisms are Shigella spp. and C. difficile (including drug-resistant forms). The ceragenins are also active against the following organisms: E. coli, Vibrios, Salmonella, Listeria monocytogenes, Campylobacteria jejuni and Yersinia enterocolitica (all Category B Pathogens). The research and development of the ceragenins falls within the field of "innate immunity" which is also listed in Class C.
描述(由申请人提供):cergenins是内源性抗菌肽的小分子模拟物。它们是广谱抗菌剂,对常见和耐药病原体具有活性。抗菌肽在控制包括胃肠道在内的多种组织中的细菌生长方面发挥着核心作用。抗菌肽已经在从人类到昆虫的各种生物中被发现,它们的普遍存在表明它们已经独立进化了无数次。这一观察结果表明,它们消灭细菌的机制提供了一种控制细菌生长的可持续手段。然而,抗菌肽的大规模制备相对困难,通常它们是蛋白酶的底物。皮草蛋白的制备相对简单,因为它们不是基于多肽,所以它们不是蛋白酶的底物。在多个直接比较角曲菌素和选定的抗菌肽,其作用机制是难以区分的。肠道感染每年夺去数百万人的生命,阻碍数千万儿童的发育,延长住院时间,增加住院病人的死亡率,并且由于水和食物受到污染而成为生物恐怖主义的潜在手段,已成为一个令人关切的问题。引起肠道感染的耐药病原体的出现加剧了这一担忧,并促使人们呼吁开发不会产生耐药性的新型抗菌素。绿皮菊素对肠道病原体有活性,口服耐受性良好。迈向临床应用的步骤包括大规模合成、配方、毒性和药效研究。建议采取这些步骤。此外,特定的cergenins对某些临床分离的艰难梭菌(Clostridium difficile)表现出非常高的活性,预计对cergenins进行微小的修饰将产生对这种人类病原体具有广泛选择性活性的化合物。提出了与艰难梭菌膜相互作用的研究和适度的结构-活性研究,以更好地靶向艰难梭菌。相关性(见说明书):目标生物是志贺氏菌和艰难梭菌(包括耐药形式)。绿皮菌素对下列生物也有活性:大肠杆菌、弧菌、沙门氏菌、单核增生李斯特菌、空肠弯曲菌和小肠结肠炎耶尔森菌(均为B类病原体)。皮曲霉素的研究和开发属于“先天免疫”领域,也属于C类。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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PAUL B SAVAGE其他文献

PAUL B SAVAGE的其他文献

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{{ truncateString('PAUL B SAVAGE', 18)}}的其他基金

Carbohydrate epitope discovery via chemical synthesis
通过化学合成发现碳水化合物表位
  • 批准号:
    10549645
  • 财政年份:
    2023
  • 资助金额:
    $ 146.77万
  • 项目类别:
Development of Novel Antimicrobial Peptide Mimics
新型抗菌肽模拟物的开发
  • 批准号:
    7645275
  • 财政年份:
    2009
  • 资助金额:
    $ 146.77万
  • 项目类别:
Development of Novel Antimicrobial Peptide Mimics
新型抗菌肽模拟物的开发
  • 批准号:
    7928810
  • 财政年份:
    2009
  • 资助金额:
    $ 146.77万
  • 项目类别:
Th1/Th2 Glycolipid Adjuvants
Th1/Th2 糖脂佐剂
  • 批准号:
    7329678
  • 财政年份:
    2008
  • 资助金额:
    $ 146.77万
  • 项目类别:
DEVELOPMENT OF NEW LIPID A BINDING AGENTS
新型脂质A结合剂的开发
  • 批准号:
    6386537
  • 财政年份:
    1998
  • 资助金额:
    $ 146.77万
  • 项目类别:
DEVELOPMENT OF NEW LIPID A BINDING AGENTS
新型脂质A结合剂的开发
  • 批准号:
    6017094
  • 财政年份:
    1998
  • 资助金额:
    $ 146.77万
  • 项目类别:
DEVELOPMENT OF NEW LIPID A BINDING AGENTS
新型脂质A结合剂的开发
  • 批准号:
    6181201
  • 财政年份:
    1998
  • 资助金额:
    $ 146.77万
  • 项目类别:
DEVELOPMENT OF NEW LIPID A BINDING AGENTS
新型脂质A结合剂的开发
  • 批准号:
    2608975
  • 财政年份:
    1998
  • 资助金额:
    $ 146.77万
  • 项目类别:
DEVELOPMENT OF NEW LIPID A BINDING AGENTS
新型脂质A结合剂的开发
  • 批准号:
    6519764
  • 财政年份:
    1998
  • 资助金额:
    $ 146.77万
  • 项目类别:
TOTAL SYNTHESIS OF MANZAMINE A
曼扎胺 A 的全合成
  • 批准号:
    2105849
  • 财政年份:
    1995
  • 资助金额:
    $ 146.77万
  • 项目类别:

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