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Updated: May 30, 2026

A Fluorescent Screening Assay for Identifying Modulators of GIRK Channels
Published on: April 24, 2012
N-imidazolebenzyl-histidine substitution in somatostatin and in its octapeptide analogue modulates receptor
Judit Erchegyi1, Renzo Cescato, Beatrice Waser
1The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.
Abstract:
Despite 3 decades of focused chemical, biological, structural, and clinical developments, unusual properties of somatostatin (SRIF, 1) analogues are still being uncovered. Here we report the unexpected functional properties of 1 and the octapeptide cyclo(3-14)H-Cys-Phe-Phe-Trp(8)-Lys-Thr-Phe-Cys-OH (somatostatin numbering; OLT-8, 9) substituted by imBzl-l- or -d-His at position 8. These analogues were tested for their binding affinity to the five human somatostatin receptors (sst(1-5)), as well as for their functional properties (or functionalities) in an sst(3) internalization assay and in an sst(3) luciferase reporter gene assay. While substitution of Trp(8) in somatostatin by imBzl-l- or -d-His(8) results in sst(3) selectivity, substitution of Trp(8) in the octapeptide 9 by imBzl-l- or -d-His(8) results in loss of binding affinity for sst(1,2,4,5) and a radical functional switch from agonist to antagonist.
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