Contribution of the amino terminal tyrosine to the interaction of gamma-endorphin with opiate receptors.
The putative behavioral hexadecapeptide, des-Tyr1-gamma-endorphin, has been compared with gamma-endorphin in an in vitro radioreceptor assay utilizing [3H] beta-endorphin as the labeled ligand and rat brain membranes as a source of opiate receptors. Under the conditions used, beta-endorphin and gamma-endorphin exhibit Kd's of 0.4 nM and 58 nM, respectively. The Kd of des-Tyr1-gamma-endorphin was estimated to be 42 micro M indicating that the amino terminal tyrosine in gamma-endorphin contributes about -4 kcal/mol at 30 degrees C to free energy of binding associated with the peptide-opiate receptor interaction. Circular dichroic spectra were obtained, and the only structural element discernible was a possible beta-turn. Thus, at physiological levels it seems unlikely that the des-Tyr1 fragment of gamma-endorphin will exhibit any significant interaction with the opiate receptor.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002942:Circular Dichroism; D004723:Endorphins / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014443:Tyrosine; D001615:beta-Endorphin; D018823:gamma-Endorphin
D004723:Endorphins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D014443:Tyrosine; D001615:beta-Endorphin; D018823:gamma-Endorphin; C018903:gamma-endorphin, des-Tyr(1)-