Structure-activity relationship study between Ornithyl-Proline and Lysyl-Proline based tripeptidomimics as angiotensin-converting enzyme inhibitors.
A designed library of tripeptidomimics of Ornithyl-Proline (Orn-Pro) and Lysyl-Proline (Lys-Pro) conjugated with various unnatural amino acids and carboxylic acid derived heterocyclics was synthesized and screened for possible inhibitors of angiotensin-converting enzyme (ACE). Among the tripeptidomimics 10[MTP-Orn-Pro], 11[HTP-Orn-Pro], 14[TA-Orn-Pro] and 20[BPA-Orn-Pro] showed prominent inhibition with IC50 values in micromolar concentrations. Structure-activity relationship study indicated that C3 side chain of Orn as compared to C4 side chain of Lys at P1' position was better suited to inhibit ACE, with propionic acid (C3) derived heterocyclics and unnatural amino acids.
Pavar
Mahesh Chand
MC
Peptide Synthesis Lab, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
Hanif
Kashif
K
Azam
Amir
A
Lata
Sneh
S
Qadar Pasha
M A
MA
Pasha
Santosh
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D007668:Kidney / Q000378:metabolism; D008239:Lysine / Q000737:chemistry; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D009952:Ornithine / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D011392:Proline; D009952:Ornithine; D008239:Lysine