The conformation of hormonal peptides in solution
For large hormonal peptides such as insulin it seems reasonable to assume that the molecules will have a fairly well-defined three-dimensional structure in solution where the groups are organised, to a large extent, into a conformation suitable for a favourable interaction with its receptor. When one considers much smaller hormonal peptides such as the linear peptides thyrotropin releasing factor (TRF), gastrin tetrapeptide and luteinising hormone releasing hormone (LH — RH) and the cyclic neurohypophysial hormones, oxytocin and lysine vasopressin, it is of interest to ask if these molecules also exist in some strongly preferred conformation in solution. Some workers have argued that the most populated conformation of the hormone will bind with the highest affinity to the receptor, although there is no a priori reason for believing this to be the case. At the present time there are no available data on hormone conformations in hormone — receptor complexes on which to examine these claims. However, the X-ray structures of several enzyme — coenzyme and enzyme — inhibitor complexes indicate that conformational changes often occur on complex formation. If there is a conformational change when the hormonal peptides bind to their receptors, then it will be necessary to define the conformational state for both the free and bound peptides if we are to fully understand the energetics of the hormone — receptor interaction.
KeywordsHormonal Peptide Fractional Population Molecular Hydrogen Bond Shift Coefficient Pseudocontact Shift
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