Campbell R M, Lee Y, Rivier J, Heimer E P, Felix A M, Mowles T F
Department of Animal Science, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Peptides. 1991 May-Jun;12(3):569-74. doi: 10.1016/0196-9781(91)90103-v.
GH-releasing activity in vitro was directly correlated with GRF receptor binding affinity for all hGRF analogs examined. hGRF(1-29)-NH2 analogs with Ala15-substitution (for Gly15) displayed 4-5 times higher affinity for the GRF receptor relative to hGRF(1-44)-NH2. Replacement of Gly15 with Sar15 resulted in a dramatic loss of activity and receptor binding. The present data supports the proposal that Ala15-substitution increases receptor affinity, and hence potency, due to increased amphiphilic alpha-helical interactions. Fragments of hGRF, representative of DPP-IV and trypsin-like cleavage, are inactive as a consequence of greatly diminished GRF receptor binding. These results provide a comprehensive analysis of the structural features required for both GRF receptor binding and activation.
对于所有检测的人促生长激素释放因子（hGRF）类似物，体外促生长激素（GH）释放活性与GRF受体结合亲和力直接相关。与hGRF(1 - 44)-NH2相比，Ala15取代（取代Gly15）的hGRF(1 - 29)-NH2类似物对GRF受体的亲和力高4 - 5倍。用Sar15取代Gly15导致活性和受体结合显著丧失。目前的数据支持这样的观点，即Ala15取代由于两亲性α-螺旋相互作用增加而提高了受体亲和力，从而增强了效力。hGRF的片段，代表二肽基肽酶-IV（DPP-IV）和类胰蛋白酶裂解产物，由于GRF受体结合大大减少而无活性。这些结果对GRF受体结合和激活所需的结构特征进行了全面分析。
