- Fine-tuning the π-π Aromatic interactions in peptides: Somatostatin analogues containing mesityl alanine
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Going through the motions: Somatostatin analogues having greater conformational rigidity than somatostatin have been prepared by substituting Phe residues in the native sequence with mesityl alanine (Msa; see structure). The analogues show high affinity f
- Martin-Gago, Pablo,Gomez-Caminals, Marc,Ramon, Rosario,Verdaguer, Xavier,Martin-Malpartida, Pau,Aragon, Eric,Fernandez-Carneado, Jimena,Ponsati, Berta,Lopez-Ruiz, Pilar,Cortes, Maria Alicia,Colas, Begona,MacIas, Maria J.,Riera, Antoni
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supporting information; experimental part
p. 1820 - 1825
(2012/04/04)
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- N-Imidazolebenzyl-histidine substitution in somatostatin and in its octapeptide analogue modulates receptor selectivity and function
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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-Trp8-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 (sst1-5), as well as for their functional properties (or functionalities) in an sst3 internalization assay and in an sst3 luciferase reporter gene assay. While substitution of Trp8 in somatostatin by imBzl-l- or -d-His8 results in sst3 selectivity, substitution of Trp8 in the octapeptide 9 by imBzl-l- or -d-His8 results in loss of binding affinity for sst1,2,4,5 and a radical functional switch from agonist to antagonist.
- Erchegyi, Judit,Cescato, Renzo,Waser, Beatrice,Rivier, Jean E.,Reubi, Jean Claude
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supporting information; experimental part
p. 5981 - 5987
(2011/10/31)
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