Erchegyi, Judit; Cescato, Renzo; Waser, Beatrice; Rivier, Jean E; Reubi, Jean-Claude (2011). N-imidazolebenzyl-histidine substitution in somatostatin and in its octapeptide analogue modulates receptor selectivity and function. Journal of medicinal chemistry, 54(17), pp. 5981-7. Easton, Pa.: American Chemical Society 10.1021/jm200307v
Full text not available from this repository.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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
Cescato, Renzo, Waser, Beatrice, Reubi-Kattenbusch, Jean-Claude |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
0022-2623 |
Publisher: |
American Chemical Society |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 14:18 |
Last Modified: |
05 Dec 2022 14:05 |
Publisher DOI: |
10.1021/jm200307v |
PubMed ID: |
21806016 |
Web of Science ID: |
000294385700002 |
URI: |
https://boris.unibe.ch/id/eprint/5553 (FactScience: 210307) |
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