title: A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain.
abstract: Sulfamoylation of the L-ornithine methyl ester side-chain generates a non-natural arginine isostere which can be coupled with N-Fmoc-L-proline to synthesize analogues which maintain the structural characteristics of the biologically important Pro-Arg dipeptide sequence. As a probe of its biological importance, the sulfamoylated amino acid derivative was also incorporated as P1 residue in tripeptide structures matching the C-terminal subsequence of fibrinogen. The reported results demonstrate that the functionalization of L-ornithine side-chain with a neutral sulfamoyl group can generate an arginine bioisostere which can be used for the synthesis of prototypes of a new class of human thrombin inhibitors.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via P. Bucci, Cubo 15/C, 87036 Arcavacata di Rende (CS), Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: De Marco
authors.forename: Maria L
authors.initials: ML
authors.lastname: Di Gioia
authors.forename: Antonella
authors.initials: A
authors.lastname: Leggio
authors.forename: Angelo
authors.initials: A
authors.lastname: Liguori
authors.forename: Francesca
authors.initials: F
authors.lastname: Perri
authors.forename: Carlo
authors.initials: C
authors.lastname: Siciliano
authors.forename: Maria C
authors.initials: MC
authors.lastname: Viscomi
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D006860:Hydrogen Bonding; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009952:Ornithine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D010314:Partial Thromboplastin Time; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors; D013918:Thrombin Time
chemical_list: D000925:Anticoagulants; D004151:Dipeptides; C550457:Nalpha-9-fluorenylmethoxycarbonyl-Ndelta-sulfamoyl(benzyloxycarbonyl)-ornithine methyl ester; D009842:Oligopeptides; D013449:Sulfonamides; C045406:prolylarginine; C088360:phenylalanylproline; D001120:Arginine; D009952:Ornithine; D013917:Thrombin