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

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- 最近，国际抗菌素耐药性研究所将抗菌素耐药性确定为人类面临的三大威胁之一， 21世纪世纪。阳离子宿主防御肽（HDP）是小的阳离子两亲性肽，并且是一种抗- 是先天免疫系统的重要组成部分。然而，HDPs具有显著的缺点，例如suscep- 对酶降解的敏感性、低至中等的活性以及它们不方便的优化。 我们最近开发了一类新的序列特异性肽模拟物，称为“α-AA肽”。在公元- 除了其固有的优点，包括增强的抗蛋白水解的稳定性和无限的潜力， 化学修饰，一些有效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， 显示出强抗炎活性。此外，一种先导化合物已显示出有效的体内活性 在小鼠模型中抗MRSA。我们的初步数据表明，抗微生物α-AA肽模拟全球 AMP的结构、功能和作用机制。这些发现强烈提示α-AA肽可能是一种新的抗肿瘤肽。 抗生素开发的途径。这里的目标是合成，开发和评估更有效的 先前设计的抗微生物环状脂化α-AA肽的类似物。我们将设计和合成新的- 先前设计的抗微生物环状脂化α-AA肽的el类似物，包括环状脂化α-AA肽， AA肽具有不同长度的烷基尾，不同的阳离子和疏水基团以及环- 将脂化α-AA肽转化为具有新型骨架的新型环状脂化肽模拟物。所有的活力- 需要通过HPLC分析和纯化。因此，配备有分析型和制备型两者的HPLC 模块（沃茨1525 EF）对我们提出的研究至关重要。

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.