Major contribution of the basic amino acid lysine at position 11 to the bioactivity of ACTH in purified isolated rat adrenocortical cells.
The contribution of the positive charge of lysine in position 11 of ACTH to the corticosteroidogenicity was tested in a purified isolated rat adrenal cell assay. ACTH analogues with Lys11 or Arg11 had the same bioactivity. Replacement of lysine by norleucine or protection of its positive charge diminished the potency by about a factor of 80. The extent of this reduction has been discussed in relation to the importance of the basic amino acid sequence 15-18 of the peptide. The result suggests a ten times higher contribution of Lys11 to the bioactivity of ACTH than the surmised potency of the individual amino acids present in the sequence 15-18.
Division of Endocrinology and Reproduction (III), Catholic University, Nijmegen, The Netherlands.
H J
HJ
Goverde
G J
GJ
Pesman
A G
AG
Smals
D000302:Adrenal Cortex / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001681:Biological Assay; D002412:Cations; D002478:Cells, Cultured; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship
D002412:Cations; D000324:Adrenocorticotropic Hormone; D008239:Lysine