RESUMEN
For the purpose of analytical investigation and structure/activity relationships, some secretin analogues and secretin fragments have been synthesized. HPLC comparison of the synthesized products with our synthetic secretin revealed about 2% [D-Ala17]secretin, 1% [D-Leu13]secretin and less than 1% aminoterminal degradation products. The D-Ala17 content can be eliminated if the starting material used for segment coupling (Z-Arg(Z2)-Asp(OBut)-Ser(But)-Ala-OH) has no D-Ala-contamination. In addition, traces of the rearrangement products [3-aspartoyl]-secretin and [beta-Asp3]secretin are suspected. Secretin can be degraded to several compounds by chromatography on a strong basic ion exchanger in 1% acetic acid. These products are more polar than secretin and have no biological activity. The secretin content measured by HPLC correlated well with the biological data, since the degradation products and other byproducts separated by HPLC have only a negligible influence on the pancreatic flow.
Asunto(s)
Secretina/análogos & derivados , Secretina/síntesis química , Secuencia de Aminoácidos , Animales , Bioensayo , Perros , Jugo Pancreático/efectos de los fármacos , Jugo Pancreático/metabolismo , Fragmentos de Péptidos/síntesis química , Secretina/farmacología , Relación Estructura-ActividadRESUMEN
The synthesis of secretin does not offer fundamental difficulties any longer. The problem of the stability of the hormone seems to be solved from a practical point of view. However, the mechanism of the inactivation of secretin in solution is not yet satisfactorily explained, alpha-beta Rearrangement of the Asp-Gly bond may play a role, but some observations indicate that inactivation is not a straight reaction. Like secretion [Ala-4] secretin shows beta-sympathomimetic activity. The availability of a suitable depot preparation permits physiological studies with secretin and its analogues after subcutaneous administration.