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

肽与层状脂质双层的相互作用机制：C3A PEPT 的变体

• 批准号: 8362174
• 负责人: Cheryl R Kuske
• 金额: $ 0.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362174
• 关键词: Antibiotics; Bacteria; Bacterial Infections; Cells; Charge; Complement 3a; Coupled; Data; Defect; Descriptor; Funding; Grant; Human; Hydrophobicity; Incidence; Knowledge; Lipid Bilayers; Membrane; Multi-Drug Resistance; National Center for Research Resources; Pattern; Peptide Library; Peptides; Principal Investigator; Radiation; Research; Research Infrastructure; Resistance; Resources; Screening procedure; Source; Structure; System; United States National Institutes of Health; Variant; Work; antimicrobial peptide; base; cost; improved; interest; membrane activity; structural biology

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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 细菌感染中多药耐药性的越来越多的问题引起了对新型抗生素的需求。这种需求反过来促使人们对抗菌肽（AMP）的兴趣增加。已经发现，这种肽的作用很快，并且当前数据还表明细菌仅对抗菌肽产生有限的耐药性。但是，这种肽的一个问题是选择性问题。肽对细菌有效，但也对人类细胞有害。使用诸如筛选文库和从其他物种中确定的肽之类的方法，已经致力于这个问题。 我们的建议旨在研究如何将抗菌肽的作用与结构描述符相结合，例如净电荷，疏水性和二级结构模式，以提高功效。我们的重点将是关于C3A衍生的肽CNY21及其变体CNY21L和CNY21K的融合替代机制的新知识。目前，CNY21及其变体的机制尚不清楚。可能性包括从包装缺陷到毛孔形成的任何东西，甚至可能像膜变薄一样简单。对于这个项目，我们建议在高度排列的多层肽膜系统上使用小角度X射线衍射（SAXD）和放牧的小角度X射线散射（GISAXS），以阐明这些新的抗菌肽的膜活性的结构基础。