Somatostatin receptor 1 selective analogues: 2. Nα- methylated scan

Abstract

Des-AA1,2,5-[D-Trp8/D-Nal8,IAmp 9] SRIF (AA = amino acid, Nal = 3-(2-naphthyl)-alanine, IAmp = 4-(N-isopropyl)-aminomethylphenylalanine, SRIF = somatostatin), with or without a tyrosine or monoiodotyrosine, were scanned with the introduction of a backbone N-methyl group and tested for binding affinity at the five human somatostatin receptors (sst1-5). Nα-Methylation resulted in loss of sst affinity (2- to >5-fold) when introduced at residues Lys4 (6), Phe6 (7), Phe7 (8), Thr10 (11), and Phe11 (12) of the parent compound Des-AA1,2,5-[D-Nal 8,IAmp9]SRIF (4). Nα-Methylation was tolerated at residues Cys3 (5), D-Nal8 (9), Thr 12 (13), and Cys14 (15) with retention of binding sst affinity and sel..