Georgsson Jennie, Rosenström Ulrika, Wallinder Charlotta, Beaudry Hélène, Plouffe Bianca, Lindeberg Gunnar, Botros Milad, Nyberg Fred, Karlén Anders, Gallo-Payet Nicole, Hallberg Anders
Department of Medicinal Chemistry, Division of Organic Pharmaceutical Chemistry, Uppsala University, PO Box 574, SE-751 23 Uppsala, Sweden.
Bioorg Med Chem. 2006 Sep 1;14(17):5963-72. doi: 10.1016/j.bmc.2006.05.019. Epub 2006 Jun 5.
Two pentapeptides, Ac-Tyr-Ile-His-Pro-Phe/Ile, were synthesized and shown to have angiotensin II AT2 receptor affinity and agonistic activity. Based on these peptides, a new series of 13 pseudopeptides was synthesized via introduction of five different turn scaffolds replacing the Tyr-Ile amino acid residues. Pharmacological evaluation disclosed subnanomolar affinities for some of these compounds at the AT2 receptor. Substitution of Phe by Ile in this series of ligands enhanced the AT2 receptor affinity of all compounds. These results suggest that the C-terminal amino acid residues can be elaborated on to enhance the AT2 receptor affinity in truncated Ang II analogues.
合成了两种五肽，即Ac-Tyr-Ile-His-Pro-Phe/Ile，并证明它们具有血管紧张素II AT2受体亲和力和激动活性。基于这些肽，通过引入五种不同的转角支架取代Tyr-Ile氨基酸残基，合成了一系列新的13种拟肽。药理学评价显示，其中一些化合物对AT2受体具有亚纳摩尔亲和力。在这一系列配体中，用Ile取代Phe增强了所有化合物对AT2受体的亲和力。这些结果表明，可以对C末端氨基酸残基进行修饰，以增强截短的Ang II类似物对AT2受体的亲和力。
