PEPTIDE INTERACTION MECHANISM WITH LAMELLAR LIPID BILAYERS: VARIANTS OF C3A PEPT

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 细菌感染中越来越多的多重耐药问题产生了对新型抗生素的需求。这种需求反过来又促使人们对抗菌肽(AMP)产生了更大的兴趣。研究发现，这类多肽的作用速度很快，目前的数据还表明，细菌对抗菌肽只产生有限的耐药性。然而，这种多肽的一个问题是选择性的问题。这些多肽对细菌有效，但对人体细胞也有害。在这个问题上已经投入了大量的工作，使用的方法包括筛选从其他物种鉴定的文库和多肽。我们的建议旨在研究如何将抗菌肽的作用与结构描述符(如净电荷、疏水性和二级结构模式)结合起来以提高疗效。我们的重点将是产生关于C3a衍生多肽CNY21及其变体CNY21L和CNY21K并入板层脂双层的替代机制的新知识。目前，CNY21及其变种的机制尚不清楚。可能性包括从填料缺陷到孔洞形成的任何事情，甚至可能像膜变薄一样简单。在这个项目中，我们建议使用小角X射线衍射(SAXD)和掠入射小角X射线散射(GISAXS)相结合的方法对高度排列的多层膜系统进行研究，以阐明这些新的抗菌肽的膜活性的结构基础。

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. Mounting problems of multidrug resistance in bacterial infections has produced a need for new types of antibiotics. This need has in turn prompted an augmented interest in antimicrobial peptides (AMP). It has been found that such peptides are fast in their action, and current data also indicate that bacteria only develop limited resistance against antimicrobial peptides. One problem with such peptides, however, is the issue of selectivity. The peptides are efficient against bacteria but also harmful to human cells. Much work has been devoted to this issue, using approaches such as screening libraries and peptides identified from other species. Our proposal aims to investigate how the action of antimicrobial peptides can be coupled with structural descriptors, such as net charge, hydrophobicity, and secondary structure patterns to improve efficacy. Our focus will be generating new knowledge regarding the incorporation alternative mechanism of C3a-derived peptide CNY21 and its variants CNY21L and CNY21K into lamellar lipid bilayers. The mechanism for CNY21 and its variants is, at the moment, unclear. Possibilities include anything from packing defects to pore formation, and may even be as simple as membrane thinning. For this project we propose to use a combination of small angle x-ray diffraction (SAXD) and grazing incidence small-angle x-ray scattering (GISAXS) on highly aligned multi-lamellar peptide membrane systems to elucidate the structural basis of the membrane activity of these new antimicrobial peptides.