Structural and conformational properties of peptides interacting with the glutathione receptor of hydra

We have made a detailed investigation of structure-activity relationships of the glutathione-induced feeding response in the fresh water coelenterate, Hydra attenuata, to map structural and conformational properties of feeding response agonists. We find that the γ-glutamyl residue of glutathione contains essential binding sites for receptor interaction, without which antagonistic as well as agonistic properties are lost. Any structural alteration which perturbs either the α-amino or the α-carboxyl group or their relative spatial orientations within the peptide has yielded an inactive derivative. An absolute requirement for activation of the receptor is a second-residue side chain of the appropriate size; analogues with second-residue side chains too large or too small are inhibitory. On the basis of the activity of conformational analogues of glutathione, torsional angles for the second residue equal to those of a right-handed α-helix are compatible with stimulus generation.