Mutational analysis of evolutionarily conserved ACTH residues.

General and comparative endocrinology (2004-02-26)
Jessica L Costa, Stephanie Bui, Peggy Reed, Robert M Dores, Miles B Brennan, Ute Hochgeschwender

alpha-Melanocyte stimulating hormone (MSH) and adrenocorticotropin (ACTH)1-24, the minimal ACTH sequence required for full activity, differ only by the 10 C-terminal amino acids of ACTH1-24. Interestingly, these ten C-terminal residues have been highly conserved throughout vertebrate evolution. To understand the functional constraints of these 10 amino acids we analyzed the effects of mutating these residues on steroidogenic activity in vivo and in vitro. Alanine substitutions of some of the first four amino acid residues (the basic core residues KKRR, 15-18) greatly reduces ACTH activity in vitro and in vivo; replacement of mutant alanines at residues 15 and 17 with glutamine residues partially restores ACTH activity. Thus, for ACTH receptor binding and activation, the amino acid residues 15-18 are important for their side chains. Surprisingly, conversion of the five C-terminal residues (20-24) to alanines increases ACTH activity in vivo over that of native ACTH. With respect to receptor binding and activity, the last five amino acid residues are important only for the peptide length they contribute; however, with respect to serum stability, their side chains are significant.

Product Number
Product Description

ProteoMass ACTH Fragment 18-39 MALDI-MS Standard, vial of 10 nmol, monoisotopic mol wt 2,464.1989 Da
Adrenocorticotropic Hormone Fragment 18-39 human, ≥97% (HPLC)

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