Structure/activity characterization of glucagon-like peptide-1.
Glucagon-like peptide-1 is a gastrointestinal hormone that strongly stimulates insulin release via specific receptors on the pancreatic beta-cell. To characterize the side-chain groups required for interaction of glucagon-like peptide-1 with its receptor, we performed binding studies with alanine-substituted glucagon-like peptide-1 analogues on RINm5F insulinoma cells. The binding affinity and biological activity of glucagon-like peptide-1 have been found to be sensitive to alanine exchanges in the N-terminal positions 1, 4, 6 and the C-terminal positions 22 and 23. Alanine substitutions at positions 5, 8, 10-12, 14, 16-21 and 25-30 do not change receptor affinity. These findings could be exploited to design glucagon-like peptide-1 agonists and probably antagonists for further physiological studies.
I. Department of Medicine, Christian-Albrechts-University, Kiel, Germany.
B
B
Gallwitz
M
M
Witt
G
G
Paetzold
C
C
Morys-Wortmann
B
B
Zimmermann
K
K
Eckart
U R
UR
Fölsch
W E
WE
Schmidt
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000096:biosynthesis; D005934:Glucagon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007340:Insulinoma / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D018027:Receptors, Glucagon; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000378:metabolism
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010446:Peptide Fragments; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP