A new non-natural arginine-like amino acid derivative with a sulfamoyl group in the side-chain

作者：De Marco Rosaria; Di Gioia Maria L; Leggio Antonella; Liguori Angelo^*; Perri Francesca; Siciliano Carlo; Viscomi Maria C

来源：Amino Acids, 2010, 38(3): 691-700.

DOI：10.1007/s00726-009-0267-2

• Ornithine
• Sulfamoyl group
• Arginine bioisosteres
• Tripeptides
• Thrombin inhibitors
• Anticoagulants

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.

• 出版日期2010-3