Assembly of Hydrolytic PeptideMetalloPorphyrin Complexes

水解肽金属卟啉配合物的组装

• 批准号: 6836163
• 负责人: NATHAN W LUEDTKE
• 金额: $ 4.3万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6836163
• 关键词: DNA; SDS polyacrylamide gel electrophoresis; chemical binding; chemical conjugate; chemical synthesis; combinatorial chemistry; fluorescence resonance energy transfer; hydrolysis; metalloporphyrins; nucleic acid purification; peptide library; postdoctoral investigator; rare earth element

DESCRIPTION (provided by applicant): Novel peptide-porphyrin-lanthanide ternary complexes are proposed for the rapid and selective hydrolysis of human telomeric DNA. Protoporhyrin IX is presented as a unique, and underutilized, scaffold for the assembly of multicomponent combinatorial libraries. Libraries of peptide-porphyrin conjugates will be synthesized and screened for their ability to bind to a telomeric quadruplex DNA with high affinity and high specificity. In parallel to this, porphyrin-lanthanide complexes that hydrolytically cleave telomeric DNA will also be developed. The diverse functional groups present on protoporphyrin IX will allow for the synthesis of peptide-porphyrin-lanthanide ternary complexes that should retain both high telomere affinity/specificity as well as hydrolytic activity. These complexes, once characterized, should provide new insight into the basic principals involved in telomere recognition and hydrolysis, and may also provide new tools to study telomere function.

描述（由申请人提供）：提出了新型的肽 - 孢子林链霉素三元复合物，以用于人端粒DNA的快速和选择性水解。 Protoporhyrin IX作为组装多组分组合库的组装是一种独特的，未充分利用的脚手架。将合成并筛选肽 - 卟啉缀合物的库，以与具有高亲和力和高特异性结合的端粒四链体DNA结合。与此相关的是，还将开发出水解端粒DNA的卟啉兰酰胺复合物。原源性IX上存在的各种官能团将允许合成肽 - 卟啉 - 兰酰胺三元络合物，这些络合物应保留高端粒亲和力/特异性以及水解活性。这些复合物一旦表征，应提供对端粒识别和水解涉及的基本原理的新见解，并且还可能提供研究端粒功能的新工具。