ACYCLIC PROTEGRIN ANALOGUES AS ANTIMICROBIAL AGENTS

作为抗菌剂的无环保护蛋白类似物

• 批准号: 7381337
• 负责人: DEWAYNE LOGAN
• 金额: $ 2.81万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381337
• 关键词: ACYCLIC; PROTEGRIN; ANALOGUES; ANTIMICROBIAL; AGENTS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Protegrins are acyclic, cysteine containing beta-sheet peptides that have shown extremely broad-spectrum antimicrobial activity, killing a diverse array of microorganisms. Because resistance is appearing to even the most potent antibiotics, the development of new antimicrobial peptides is imperative. Non-cysteine protegrin analogues are being synthesized to minimize oxidation and difficult deprotection of the disulfide linkage. The PI's long-term goal is to elucidate the necessary amino acid residues affecting the bioactivity of the as necessary prerequisite to the development of non-cysteine peptides as therapeutic agents. The specific hypothesis is that the incorporation of substituted guanidine residues and quaternary ammonium groups would increase the bioactivity of these analogues. This hypothesis is based on the observations that 1) substituted guanidine residues can facilitate binding to complex receptors and 2) quaternary ammonium compounds serve as disinfectants, antiseptics, and preservatives. Based on these observations, the focus is to design new antimicrobial peptides. The specific aims are: 1. Synthesis of non-cysteine peptide analogues incorporated with fully substituted guanidine residues and quaternary ammonium groups. The analogues will be synthesized using standard Fmoc deprotection chemistry on an automated solid phase synthesizer. 2. Elucidation of the secondary structure of the non-cysteine peptide analogues. The amphipathic structures will be elucidated using circular dichroism analysis to determine any change from the original beta-sheet structure. 3. Confirmation of bioactivity of non-cysteine peptide analogues. The bioactivity of the analogues will be tested on various microorganisms using minimum inhibitory concentration (MIC) protocols.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。Protegrins是无环的、含有半胱氨酸的β折叠肽，其显示出极其广谱的抗微生物活性，杀死多种微生物。由于即使是最有效的抗生素也出现了耐药性，因此开发新的抗菌肽势在必行。合成非半胱氨酸保护蛋白类似物以最小化二硫键的氧化和难以脱保护。PI的长期目标是阐明影响生物活性的必要氨基酸残基，作为开发非半胱氨酸肽作为治疗剂的必要前提。具体的假设是，取代的胍残基和季铵基团的掺入将增加这些类似物的生物活性。该假设基于以下观察结果：1）取代的胍残基可促进与复合受体的结合，2）季铵化合物可用作消毒剂、防腐剂和防腐剂。基于这些观察，重点是设计新的抗菌肽。 具体目标是：1.合成并入有完全取代的胍残基和季铵基团的非半胱氨酸肽类似物。将在自动固相合成仪上使用标准Fmoc脱保护化学合成类似物。2.非半胱氨酸肽类似物二级结构的解析。将使用圆二色谱分析来阐明两亲性结构，以确定原始β-折叠结构的任何变化。3.非半胱氨酸肽类似物生物活性的确认。将使用最小抑菌浓度（MIC）方案在各种微生物上测试类似物的生物活性。