1xy4
From Proteopedia
NMR strcutre of sst1-selective somatostatin (SRIF) analog 1
Overview
The three-dimensional NMR structures of six analogues of somatostatin (SRIF) are described. These analogues with the amino acid 4-(N-isopropyl)-aminomethylphenylalanine (IAmp) at position 9 exhibit potent and highly selective binding to human SRIF subtype 1 receptors (sst(1)). The conformations reveal that the backbones of these analogues have a hairpin-like structure similar to the sst(2)-subtype-selective analogues. This structure serves as a scaffold for retaining a unique arrangement of the side chains of d-Trp(8), IAmp(9), Phe(7), and Phe(11) or m-I-Tyr(11) (m-I-Tyr = mono-iodo-tyrosine). The conformational preferences and results from biological analyses of these analogues(1,2) allow a detailed study of the structure-activity relationship of SRIF. The proposed consensus pharmacophore of the sst(1)-selective analogues requires a unique set of distances between an indole/2-naphthyl ring, an IAmp side chain, and two aromatic rings. This motif is necessary and sufficient to explain the binding affinities of all of the analogues studied and is distinct from the existing models suggested for sst(4) as well as sst(2)/sst(5) selectivity.
About this Structure
Full crystallographic information is available from OCA.
Reference
Somatostatin receptor 1 selective analogues: 4. Three-dimensional consensus structure by NMR., Grace CR, Durrer L, Koerber SC, Erchegyi J, Reubi JC, Rivier JE, Riek R, J Med Chem. 2005 Jan 27;48(2):523-33. PMID:15658866 Page seeded by OCA on Sat May 3 15:39:21 2008
