Enzymatic degradation studies of endomorphin-2 and its analogs containing N-methylated amino acids.
In this paper, we describe the synthesis of novel endomorphin-2 analogs, containing N-methylated amino acids, consecutively in each position. The receptor-binding profile of the new analogs and their stability against enzymatic cleavage by commercially available peptidases, carboxypeptidase Y and aminopeptidase M, and a rat brain homogenate are reported. The best analog of this series, [Sar2]endomorphin-2, was almost equipotent with the parent peptide in the mu-receptor-binding assay and was also highly resistant to enzymatic degradation. This analog may be a suitable candidate for the in vivo antinociceptive studies.
Janecka
Anna
A
Department of Medicinal Chemistry, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Kruszynski
Rafal
R
Fichna
Jakub
J
Kosson
Piotr
P
Janecki
Tomasz
T
D000478:Alkylation; D000596:Amino Acids / Q000378:metabolism*; D000626:Aminopeptidases / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D018826:CD13 Antigens; D043402:Cathepsin A / Q000378:metabolism; D004795:Enzyme Stability / Q000502:physiology; D007700:Kinetics; D008024:Ligands; D063208:Methionyl Aminopeptidases; D008745:Methylation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D051381:Rats; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D008024:Ligands; D009842:Oligopeptides; D017450:Receptors, Opioid, mu; C105294:endomorphin 2; D000626:Aminopeptidases; D063208:Methionyl Aminopeptidases; D018826:CD13 Antigens; D043402:Cathepsin A