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.

抗生素耐药性目前是最重要的公共卫生问题之一。世界健康组织 - ization最近确定抗菌抗性是面对人类面临的三个最大威胁之一 21世纪。阳离子宿主防御宠物（HDPS）是小阳离子两亲性宠物，是一种 先天免疫系统的成立和至关重要的一部分。但是，HDP具有明显的缺点，例如 酶促降解，低到中度活性及其不方便优化的能力。 我们最近开发了一种称为“α-磷酸”的新型序列特异性肽仪。在广告中 符合其内在优势，包括对蛋白水解的稳定性增强和无限潜力 化学修饰，某些潜在的分子显示广谱抗菌活性，并且不诱导 耐药病原体的明显耐药性。此外，它们还可以调节免疫反应，并且 表现出强大的抗炎活性。此外，一种铅化合物显示了体内活性的潜力 在小鼠模型中反对MRSA。我们的初步数据表明，抗菌α-酰肽模仿全球 AMP的结构，功能和机制。这些发现强烈表明α-磷酸可能是一种新的AP- 抗生素发育。这里的目的是综合，开发和评估更有效的 先前设计的抗微生物循环蛋白α-磷酸的类似物。我们将设计和合成11月 - 先前设计的抗微生物环蛋白脂化的α-肽的EL类似物，包括环状脂化的α- 烷基尾巴，潜水阳离子和疏水群的移植物和循环膨胀 脂化的α-磷酸对新的循环脂化肽仪具有新的骨架。所有的pep- 潮汐需要通过HPLC进行分析和纯化。这是与分析和制备的HPLC等效物 模块（Waters 1525EF）对于我们提出的研究至关重要。