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感兴趣。将制备天然配体神经肽Y的截短肽序列，其中两个键保留THR-32和GLN-34将被构型限制的环丁烷氨基酸代替。这些组件比环丙烷衍生的衍生物具有多个优点，这些衍生物目前是最有前途的材料。将使用一般的光化学合成策略提供指定的环丁烷氨基酸的库，这将允许对立体化学的后果和侧链功能的后果进行全面评估，以实现受体结合的效力和选择性。还将与NPY类似物进行比较，该类似物还将进行其他环状氨基酸取代。最好的配体将测试其靶向靶向富含Y1受体细胞的细胞毒性天然产物的能力。