Hormones bioactive conformations

Conformational restriction is a very powerful method for probing the bioactive conformations of peptides. Small peptides have many flexible torsion angles so that enormous numbers of conformations are possible in solution. For example, a simple tripeptide such as thyrotropin-releasing hormone (TRH 7) (Fig. 15.4) with six flexible bonds could have over 65,000 possible conformations. The number of potential conformers for larger peptides is enormous, and some method is needed to exclude potential conformers. Modem biophysical methods, e.g., X-ray crystallography or isotope edited nuclear magnetic resonance (NMR), (33) can be used to characterize peptide-protein interactions for soluble proteins, but most biophysical methods cannot yet determine the conformation of a ligand bound to constitutive receptors, e.g., G-protein-coupled receptors (34, 35). 

Potential Bioactive Conformations of Hormones of the Gastrin Family... 

As discussed in section 2.2., N-terminal extensions of the active site portion of the gastrin molecule leads to a remarkable stabilization of its potential bioactive conformation with concomitant increase of hormonal potency. This aspect has been analyzed in the case of CCK too, by using the series of peptides listed in table 2 (64). CD measurements revealed that N-terminal extensions of the CCK nv-lecule in sequence mode are affecting only marginally the conformational st s of the bioactive core. As expected from what was known for gastrin, the CD... 

Freidinger, R.M., Veber, D.F., Perlow, D.S., Brooks, J.R. and Saperstein, R. (1980) Bioactive conformation of luteinizing hormone-releasing hormone evidence fimm a conformationally constrained analog. Science 210 656-658. 

Keywords Peptide synthesis Peptide hormone Structure-activity relationship Neuropeptide Y Bioactive conformation... 

C. S. C. Wu, A. Hachimori, J. T. Yang, Lipid-induced ordered conformation of some peptide hormones and bioactive oligopeptides predominance of the helix over the beta-form. Biochemistry 1982, 21, 4556-4562. 

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