PMID: 11311064Apr 20, 2001Paper

N-Methyl scan of somatostatin octapeptide agonists produces interesting effects on receptor subtype specificity

Journal of Medicinal Chemistry
W G RajeswaranD H Coy

Abstract

The search for synthetic analogues of somatostatin which exhibit selective affinities for the five receptor subtypes is of considerable basic and therapeutic interest and has generated a large number of potent agonist analogues with a wide spectrum of binding profiles. In the past, conformational restriction of side chain groups and the peptide backbone has yielded the most interesting results. Under the latter category and as part of the present study, we were interested in the potential effects of N-methylation of peptide bond NH groups on binding affinity since this approach had not been systematically examined with these peptides. This was aided by new chemistries for introducing an N-Me group during regular solid-phase peptide synthesis using Boc protection. A number of interesting effects were noted on relative binding affinities of the two series of agonist sequences chosen, DPhe(5)(or Tyr(5))-c[Cys(6)-Phe(7)-DTrp(8)-Lys(9)-Thr(10)-Cys(11)]Thr(12)-NH(2) (SRIF numbering), at the five known human somatostatin receptors transfected into and stably expressed by CHO cells. N-Methylation of residues 7 (Phe), 10 (Thr), 11 (Cys), and 12 (Thr) largely destroyed affinities for all five receptors. N-Methylation of DTrp in the DPhe ...Continue Reading

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Citations

Apr 12, 2011·Journal of Medicinal Chemistry·Hanna AnderssonAnders Hallberg
Mar 8, 2011·Molecular Pharmaceutics·Oded OvadiaAmnon Hoffman
Jul 1, 2010·Expert Opinion on Drug Discovery·Oded OvadiaHorst Kessler
Dec 21, 2012·Chemical Biology & Drug Design·Andrew G JamiesonWilliam D Lubell
Aug 10, 2011·Chemical Biology & Drug Design·Yftah Tal-GanChaim Gilon
Aug 11, 2016·Organic Letters·Brett A HopkinsNunzio Sciammetta
Nov 23, 2017·Journal of Molecular Modeling·Roksana Wałęsa, Małgorzata A Broda
Dec 5, 2003·Nature Reviews. Drug Discovery·Gisbert WeckbeckerChristian Bruns
Oct 18, 2018·Chemistry : a European Journal·Yantao Chen
Dec 15, 2007·Chemistry : a European Journal·Jayanta ChatterjeeHorst Kessler
Sep 29, 2005·Journal of Peptide Science : an Official Publication of the European Peptide Society·Eric BironHorst Kessler
Apr 20, 2007·Chemical Biology & Drug Design·Gregory V NikiforovichSamuel Achilefu
Apr 23, 2008·Journal of Combinatorial Chemistry·Josep Farrera-SinfreuMiriam Royo
Feb 6, 2009·Journal of Medicinal Chemistry·Judit Tulla-PucheFernando Albericio

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