[12-Homoarginine]glucagon: synthesis and observations on conformation, biological activity, and copper-mediated peptide cleavage

摘要: Abstract Specific modification of the single lysine residue (Lys-12) in glucagon with O-methylisourea has been effected by blocking reactivity amino terminal histidine copper, providing a method for obtaining [12-homoarginine]glucagon. It was found that as side reaction, under conditions Cu(II) catalyzed cleavage polypeptide chain between Asp-9 and Tyr-10, Lys-12 Tyr-13. This observation may be value development sequence-specific peptide procedure. The dilute solution conformations [12-homoarginine]-glucagon were compared circular dichroism, fluorescence, phosphorescence, energy transfer, optical detection magnetic resonance. results indicate conversion to homoarginine does not alter helix content, conformation vicinity tyrosine tryptophan residues, or relative distances orientations these residues. However, reduces hormone potency towards activation lipolysis isolated rat epididymal fat cells factor seven. We attribute loss an interference specific interaction cell receptor, change hormone.