Biological activities of ACTH-analogues varied in the active site.
PMID 190838 · Acta endocrinologica · 1977 · DOI 10.1530/acta.0.0840470
Authors: J W van Nispen; G I Tesser; P L Barthe; R Maier; L Schenkel-Hulliger
Abstract
The steroidogenic and lipolytic activities of corticotrophin-(1-24)-tetracosapeptide and [Lys17,18]corticotrophin-(1-18)-octadecapeptide amide were compared with those of corresponding analogues substituted in position 8 with norarginine and homoarginine, and in position 9 with phenylalanine and pentamethylphenylalanine. The norarginine containing analogues demonstrated a rewarding activity, although they were generally somewhat less active than the homoarginine containing compounds. This confirms the previous conclusions concerning the indispensability of arginine as a guanidinium derivate. The analogues in which phenylalanine was a substitute for tryptophan, constituted partial agonists with a low activity in steroidogenesis and lipolysis but a rather high melanophore stimulating activity. Insertion of the permethylated derivative of phenylalanine in this position, which ensures the presence of an aminoacyl residue with the full electron donor properties of tryptophan, destroyed the low steroidogenic and lipolytic activity, but increased the MSH-activity about 2-fold.
Adrenal Glands; Adrenocorticotropic Hormone; Animals; Arginine; Corticosterone; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Epididymis; Fatty Acids, Nonesterified; Glycerol; Hormones; In Vitro Techniques; Lipid Metabolism; Male; Melanophores; Phenylalanine; Rabbits; Rats; Structure-Activity Relationship
Cite
J W van Nispen; G I Tesser; P L Barthe; R Maier; L Schenkel-Hulliger. Biological activities of ACTH-analogues varied in the active site. Acta endocrinologica (1977). PMID 190838. DOI 10.1530/acta.0.0840470.