Open AccessStudy of a series of analogs of salmon calcitonin in which alanine replaces leucine
Author(s) -
EPAND Richard M.,
EPAND Raquel F.,
ORLOWSKI Ronald C.
Publication year - 1990
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1990.tb15444.x
Subject(s) - alanine , chemistry , calcitonin , peptide , leucine , stereochemistry , substitution (logic) , structure–activity relationship , biochemistry , amino acid , biology , endocrinology , in vitro , computer science , programming language
Leucine residues at positions 12, 16 and 19 of salmon calcitonin were systematically replaced by alanine either one, two or three at a time. Substitution of Ala at positions 12 or 16 had the greatest effect on the structure of the peptide and on the ability of the peptide to attain structures of higher helical content in the presence of lipid. Despite the similar effects on the conformational properties, the effects on activity are markedly different for analogs with Ala substitutions at positions 12 and 16. The Ala 12 derivatives are much less active while the Ala 16 derivatives are slightly more active than the parent hormone. In contrast to the effects of substitutions at these positions, substitution of Ala at position 19 has relatively little effect on activity or on conformation. These results demonstrate that different regions of the calcitonin molecule have different conformational requirements for maximal activity.