NMR-solution structures and affinities for the human somatostatin G-protein-coupled receptors hsst 1-5 of CF 3 derivatives of Sandostatin® (octreotide)

Abstract

The previously reported (Helv. Chim. Acta 2008, 91, 2035) derivatives of octreotide (1) with a (CF 3)-Trp substitution, i.e., 3, and with open-chain structures, i.e., 2, 4, and 5, have been tested for their affinities to hsst 1-5 receptors and subjected to a detailed NMR analysis. Their affinities vary from 15 nM to 5 μM, as compared to 0.6 nM to 0.8 μM for octreotide itself (Table 1). This decreased bioactivity may have had to be expected for the open-chain compounds 4 and 5; possible reasons for this decrease in the case of CF 3 derivative of octreotide, 3, are discussed. NMRAnalysis (Tables 2 and 3) provides evidence for increased dynamics of all new derivatives 2 - 5. The dynamics of the..