Requesting HPLC for the project of "Alpha-AApeptides as a Novel Class of Antimicrobial Biomaterials"

“α-A肽作为新型抗菌生物材料”项目申请HPLC

• 批准号: 9700847
• 负责人: Jianfeng Cai
• 金额: $ 7万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9700847
• 关键词: Anti-inflammatory; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Biocompatible Materials; Cations; Chemicals; Data; Development; Evaluation; High Pressure Liquid Chromatography; Host Defense; Hydrophobicity; Immune response; Innate Immune System; Lead; Length; Moderate Activity; Modification; Peptides; Periodicity; Predisposition; Preparation; Proteolysis; Public Health; Research; Resistance; Structure; Tail; Vertebral column; Water; World Health Organization; amphiphilicity; analog; antimicrobial; design; drug resistant pathogen; in vivo; methicillin resistant Staphylococcus aureus; mouse model; novel; peptidomimetics

Antibiotic resistance is currently one of the most significant public health concerns. The World Health Organ- ization recently identified antimicrobial resistance as one of the three greatest threats facing mankind in the 21st century. Cationic host-defense peptides (HDPs) are small cationic amphiphilic peptides, and are an an- cient and vital part of the innate immune system. However, HDPs have significant drawbacks such as suscep- tibility to enzymatic degradation, low-to-moderate activity and their inconvenient optimization. We have recently developed a new class of sequence-specific peptidomimetics termed “α-AApeptides”. In ad- dition to their intrinsic advantages including enhanced stability against proteolysis and limitless potential for chemical modification, some potent molecules display broad-spectrum antimicrobial activity, and do not induce apparent resistance in drug-resistant pathogens. Furthermore, they can also modulate immune responses and show strong anti-inflammatory activity. In addition, one lead compound has shown potent in vivo activity against MRSA in mouse model. Our preliminary data suggest that antimicrobial α-AApeptides mimic the global structure, function and mechanism of AMPs. These findings strongly suggest α-AApeptides may be a new ap- proach for antibiotic development. The objective here, is to synthesize, develop and evaluation of more potent analogs of previously designed antimicrobial cyclic-lipidated α-AApeptides. We will design and synthesize nov- el analogs of previously designed antimicrobial cyclic-lipidated α-AApeptides, including cyclic-lipidated α- AApeptides with different length of alkyl tails, diverse cationic and hydrophobic groups and expansion of cyclic- lipidated α-AApeptides to new classes of cyclic-lipidated peptidomimetics with novel backbones. All the pep- tides need to be analyzed and purified by HPLC. Thus, a HPLC equipped with both analytical and preparative modules (Waters 1525EF) extremely critical for our proposed research.

抗生素耐药性是目前最重要的公共卫生问题之一。世界卫生组织