Relationship between excluded volume interactions and biological activity in D-leucine containing sequences

Here we are interested to epimerization of different residues. DNA cloning has shown that at those positions where a D-amino acid is found in the end product, a normal codon for the corresponding L-amino acid is present. This implies that the D-residue are formed from L-amino acid by a post-translational reaction. Here we report about homologues sequences of the native peptide conotoxins having L-leucine on the third amino acid from the C-terminus and the isomer with D-leucine in the same position. Our work highlight the importance of structural factors, beyond the disulfide pattern and electrostatic interactions, in the understanding of the functional properties of bioactive peptides. The latter needs to be considered when designing analogues for further applications. References 1. O. Buczek, Yoshikami Doju, M. Watkins, G. Bulaj, E.C. Jimenez, B.M. Olivera FEBS Journal (2005), 272, 4178.