Aspartimide modified galanin analogue antagonizes galanin action on insulin secretion.
Aspartimide (Asi) formation is one of the most serious side reactions that can occur both during solid phase synthesis and storage of peptides containing aspartic acid. Although numerous studies on the mechanism of Asi formation conducted so far, the problem still remains unresolved and relatively little is known about the impact of this side reaction on biological properties of such modified peptides. In the present work we characterized the effect of Asi formation on biological properties of galanin(1-15) analogue modified in position 14 with aspartic acid, investigating its action on rat isolated gastric smooth muscles and glucose-induced insulin secretion from rat isolated islets of Langerhans. Our results show that this side process may adversely affect biological properties of such modified peptides. As we expected, modification of GAL(1-15)NH(2) structure changed the interaction of GAL(1-15)NH(2) with its receptors and consequently yielded peptide which, in studies on insulin secretion, showed insulinotropic- and antagonistic activities as compared to Asi-free analogue.
Ruczyński
Jarosław
J
Department of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland. ruczynski@chem.univ.gda.pl
Konstański
Zdzisław
Z
Cybal
Magdalena
M
Kocić
Ivan
I
Rekowski
Piotr
P
D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D005260:Female; D019004:Galanin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D008297:Male; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects; D013552:Swine
D007328:Insulin; D001224:Aspartic Acid; C075871:aspartimide; D019004:Galanin