DQC CONSTRAINTS FOR STUDY OF PEPTOID STRUCTURE

用于类肽结构研究的 DQC 约束

• 批准号: 8172091
• 负责人: PETER P BORBAT
• 金额: $ 0.29万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172091
• 关键词: Amino Acids; Binding; Carbon; Complement component C1s; Computer Retrieval of Information on Scientific Projects Database; Drug Delivery Systems; Funding; Grant; Institution; Label; Measurement; Measures; Metabolic; N-substituted Glycines; Nitrogen; Peptoids; Physiologic pulse; Positioning Attribute; Relative (related person); Research; Research Personnel; Resources; Series; Side; Source; Spin Labels; Structure; Techniques; United States National Institutes of Health; Vertebral column; Work; analog; design; flexibility; functional group; interest; mutant; polypeptide; tool

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. Peptoids are amino acid analogs whose basic unit consists of N-substituted glycine derivatives. As opposed to the usual case, where the side chain is bound to the alpha-carbon, in a peptoid the side chain or functional group is bonded to the alpha-nitrogen. Relative to polypeptides, polypeptoids have their side chains shifted by one position along the backbone. Peptoids were designed as a new series of potentially bioactive compounds due to the variety of possible functional groups and the potential in drug delivery following from their expected metabolic stability. The structure of peptoids is of particular interest and has been studied extensively with NMR. For larger peptoid molecules spin-labeling techniques and large distance measurements by pulsed ESR can be routinely used in structural work. With Kirshenbaum we conducted a collaborative study on several spin-labeled peptoids. The distances were measured by DQC, which has proven to be a powerful tool for distances in the range of 11 to 70 ¿. We examined several peptoids with their side chains substituted by nitroxides. In particular, we determined the following distances for the respective peptoid mutants of AF71 labeled at the C-terminus and progressively at C1-C5 residues: AF71-C1 (12.5 ¿, fwhm 4 ¿), AF71-C2 (15.0 ¿), AF71-C3 (15.0 ¿, fwhm 4.0A), AF71-C4 (16.0¿), and AF71-C5 (18.0¿). Also AF69-D6, a peptoid of more flexible structure caused by a different side-chain, was studied. Evidence for peptoid flexibility was supported by DQC yielding an average distance of 18¿ with fwhm of 9.5 ¿.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 肽是氨基酸类似物，其基本单位由N-取代的甘氨酸衍生物组成。与通常的情况相比，侧链与α-碳结合，在肽中，侧链或官能团与α-氮结合。相对于多肽，多肽的侧链沿骨架沿一个位置移动。由于可能的功能组种类繁多，因此肽被设计为一系列潜在生物活性化合物的新系列，并且从预期的代谢稳定性中递送药物的潜力。肽的结构特别有趣，已经用NMR进行了广泛的研究。对于较大的肽分子，自旋标记技术和通过脉冲ESR进行的大距离测量可通常用于结构工作。使用Kirshenbaum，我们就几种自旋标记的肽进行了协作研究。距离通过DQC测量，事实证明，这是11至70»范围内的距离的强大工具。我们检查了几种肽，其侧链被硝基氧化物取代。特别是，我们确定了标记为C-terminus和C1-C5的AF71的各个肽突变体的以下距离：AF71-C1（12.5€，FWHM4¿），AF71-C2（AF71-C2（15.0¿） （18.0€）。另外，AF69-D6是由不同侧链引起的更灵活结构的肽。 DQC支持肽灵活性的证据，其平均距离为18.5€。