title: Structure-activity relationship study between Ornithyl-Proline and Lysyl-Proline based tripeptidomimics as angiotensin-converting enzyme inhibitors.
abstract: 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.
authors.affiliation: Peptide Synthesis Lab, Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India.
authors.forename: Mahesh Chand
authors.initials: MC
authors.lastname: Pavar
authors.forename: Kashif
authors.initials: K
authors.lastname: Hanif
authors.forename: Amir
authors.initials: A
authors.lastname: Azam
authors.forename: Sneh
authors.initials: S
authors.lastname: Lata
authors.forename: M A
authors.initials: MA
authors.lastname: Qadar Pasha
authors.forename: Santosh
authors.initials: S
authors.lastname: Pasha
mesh_terms: 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
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D011392:Proline; D009952:Ornithine; D008239:Lysine