Small-ring cyclic â-amino acids as building blocks for neuropeptide Y analogs

小环环状氨基酸作为神经肽 Y 类似物的构建模块

• 批准号: 209346066
• 负责人: Professor Dr. Oliver Reiser
• 金额: --
• 依托单位: Institut für Organische Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/209346066?language=en
• 关键词: Small; ring; cyclic; amino; acids

Selective ligands for Y1 receptors are of interest as anti-cancer drug carriers. Truncated peptide sequences of a natural ligand, Neuropeptide Y, will be prepared in which two key residues Thr-32 and Gln-34 will be replaced by conformationally restricted cyclobutane -amino acids. These components have several advantages over cyclopropane-derived derivatives, which are currently the most promising materials. A library of the designated cyclobutane -amino acids will be made available using a general photochemical synthetic strategy, which will allow full evaluation of the consequences of stereochemistry and side chain functions for the potency and selectivity of receptor binding. Comparison with NPY analogs which incorporate other cyclic -amino acid substitutions will also be made. The best ligand will be tested for its ability to target deliver a cytotoxic natural product to Y1 receptor-rich cells.

Y1受体的选择性配体作为抗癌药物载体受到关注。将制备天然配体神经肽Y的截短肽序列，其中两个关键残基Thr-32和Gln-34将被构象限制的环丁烷α-氨基酸取代。这些组分具有优于环丙烷衍生物的几个优点，环丙烷衍生物是目前最有前途的材料。将使用一般光化学合成策略来提供指定的环丁烷α-氨基酸的库，这将允许全面评估立体化学和侧链功能对受体结合的效力和选择性的影响。还将与掺入其他环状α-氨基酸取代的NPY类似物进行比较。将测试最佳配体将细胞毒性天然产物靶向递送至富含Y1受体的细胞的能力。