Synthesis of somatostatin mimetics based on 1-deoxynojirimycin.
The synthesis of novel somatostatin mimetics from 1-deoxynojirimycin (DNJ) is described. The dipeptide mimetic, which respectively displayed the side chains of tryptophan and lysine at the nitrogen and O6 atoms of the iminosugar scaffold is a ligand (K(i)=3.2 microM) for the human somatostatin receptor subtype 4 (hSSTR4) but has lower affinity (K(i)>100 microM) for hSSTR5. A benzylated analogue of the Trp-Lys mimetic displays higher affinity for hSSTR5 (K(i)=5 microM).
Chagnault
Vincent
V
Centre for Synthesis and Chemical Biology, UCD School of Chemistry and Chemical Biology, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
Lalot
Jérôme
J
Murphy
Paul V
PV
D017485:1-Deoxynojirimycin / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D006728:Hormones / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D050111:Imino Sugars / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology
D006728:Hormones; D050111:Imino Sugars; D008024:Ligands; D017481:Receptors, Somatostatin; C098681:somatostatin receptor subtype-4; D017485:1-Deoxynojirimycin; D013004:Somatostatin; D014364:Tryptophan; D008239:Lysine