Di Cianni, Alessandra; Carotenuto, Alfonso; Brancaccio, Diego; Novellino, Ettore; Reubi, Jean-Claude; Beetschen, Karin; Papini, Anna Maria; Ginanneschi, Mauro (2010). Novel octreotide dicarba-analogues with high affinity and different selectivity for somatostatin receptors. Journal of medicinal chemistry, 53(16), pp. 6188-97. Easton, Pa.: American Chemical Society 10.1021/jm1005868
Full text not available from this repository. (Request a copy)A limited set of novel octreotide dicarba-analogues with non-native aromatic side chains in positions 7 and/or 10 were synthesized. Their affinity toward the ssts1-5 was determined. Derivative 4 exhibited a pan-somatostatin activity, except sst4, and derivative 8 exhibited high affinity and selectivity toward sst5. Actually, compound 8 has similar sst5 affinity (IC50 4.9 nM) to SRIF-28 and octreotide. Structure-activity relationships suggest that the Z geometry of the double-bond bridge is that preferred by the receptors. The NMR study on the conformations of these compounds in SDS(-d25) micelles solution shows that all these analogues have the pharmacophore beta-turn spanning Xaa7-D-Trp8-Lys9-Yaa10 residues. Notably, the correlation between conformation families and affinity data strongly indicates that the sst5 selectivity is favored by a helical conformation involving the C-terminus triad, while a pan-SRIF mimic activity is based mainly on a conformational equilibrium between extended and folded conformational states.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology |
UniBE Contributor: |
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 14:09 |
Last Modified: |
05 Dec 2022 14:00 |
Publisher DOI: |
10.1021/jm1005868 |
PubMed ID: |
20666484 |
Web of Science ID: |
000280962700025 |
URI: |
https://boris.unibe.ch/id/eprint/793 (FactScience: 200865) |
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