GRF analogs and fragments: correlation between receptor binding, activity and structure.

R M Campbell; Y Lee; J Rivier; E P Heimer; A M Felix; T F Mowles

doi:10.1016/0196-9781(91)90103-v

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GRF analogs and fragments: correlation between receptor binding, activity and structure.

R M Campbell·Y Lee·J Rivier·E P Heimer·A M Felix·T F Mowles

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Abstract

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.

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Animals Growth Hormone-Releasing Hormone In Vitro Techniques Kinetics Male Peptide Fragments Pituitary Gland, Anterior Protein Conformation Rats Rats, Inbred Strains Receptors, Neuropeptide Receptors, Neurotransmitter Receptors, Pituitary Hormone-Regulating Hormone Structure-Activity Relationship Journal Article

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R M Campbell, Y Lee, J Rivier, E P Heimer, A M Felix, T F Mowles. GRF analogs and fragments: correlation between receptor binding, activity and structure.. https://doi.org/10.1016/0196-9781(91)90103-v

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