Somatostatin structure-activity relationships

Amino-acid abbreviations are spelled out in Appendix V. Through a series of structure-activity relationship studies, the bioactive conformation and peptide sequences that produce undesirable biologic responses were identihed. Also identified were sequences susceptible to proteolysis, and a working-model compound that eliminated these sequences was proposed (Figure 4.6). This allowed the rational design of optimized somatostatin analogues with desirable biologic characteristics and activity and increased stability. 

Hocart, S.J., Reddy, V., Murphy, W.A. and Coy, D.H. (1995). Three-Dimensional Quantitative Structure-Activity Relationships of Somatostatin Analogs. 1. Comparative Molecular Field Analysis of Growth Hormone Release Inhibiting Potencies. J.Med.Chem., 38,1974-1989. 

Hirschmann, Nicolaou, Smith, and coworkers introduced the use of monosaccharides as privileged structures to modulate receptor and receptor subtype affinities. The P-o-glucose scaffold serves as a nonpeptidal peptidomimetic of the hormone somatostatin (SRIF). Over the past decade, a number of analogs have been synthesized and tested to explore the structure-activity relationships of differential substitution of the sugar core. " In collaboration with Merck researchers, Hirschmann and cowoikers discovered both somatostatin and NK-1 antagonists (Figure 7.2). A small... 

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