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

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 细菌感染中的多药耐药性问题日益严重，因此需要新型抗生素。这种需求反过来又促使人们对抗菌肽（AMP）的兴趣增加。已经发现，这些肽在它们的作用中是快速的，并且目前的数据还表明细菌仅对抗微生物肽产生有限的抗性。然而，这种肽的一个问题是选择性问题。这些肽对细菌有效，但对人体细胞也有害。许多工作已经致力于这个问题，使用的方法，如筛选库和肽从其他物种。 我们的建议旨在研究抗菌肽的作用如何与结构描述符（如净电荷，疏水性和二级结构模式）相结合，以提高功效。我们的重点将是产生新的知识，关于纳入替代机制的C3 a衍生肽CNY 21及其变体CNY 21 L和CNY 21 K到层状脂质双层。目前，CNY 21及其变体的机制尚不清楚。可能包括从填充缺陷到孔形成的任何情况，甚至可能像膜变薄一样简单。对于这个项目，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）高度对齐的多层肽膜系统的组合，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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.