Conformational and biological properties of the Ala10-analog of human Des-Trp1, Nle12-minigastrin

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Abstract
Synthesis, conformation, and biological properties of the Ala10 analogue of des-Trp1,Nle12-minigastrin are reported. Replacement of the Gly residue in the original sequence with Ala remarkably changes the conformational preference of the hormone in trifluoroethaol. CD and NMR results indicate that the conformational change is mainly located in the C-terminal portion of the molecule, with probable extension of the N-terminal .alpha.-helix throughout the entire sequence. The structural modification causes a 10-fold decrease in the biological potency of the hormone, which is about as active as the C-terminal tetrapeptide amine. These findings support our prvious hypothesis that the optimal bioactive conformation of the native hormone is U-shaped, with mutual interactions among the two end segments.