A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain.
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.
De Marco
Rosaria
R
Dipartimento di Scienze Farmaceutiche, Università della Calabria, Via P. Bucci, Cubo 15/C, 87036 Arcavacata di Rende (CS), Italy.
Di Gioia
Maria L
ML
Leggio
Antonella
A
Liguori
Angelo
A
Perri
Francesca
F
Siciliano
Carlo
C
Viscomi
Maria C
MC
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
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