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

Sulfamoylation of the L-ornithine methyl esterside-chain generates a non-natural arginine isostere whichcan be coupled with N-Fmoc-L-proline to synthesize analogueswhich maintain the structural characteristics of thebiologically important Pro-Arg dipeptide sequence. As aprobe of its biological importance, the sulfamoylatedamino acid derivative was also incorporated as P1 residuein tripeptide structures matching the C-terminal subsequenceof fibrinogen. The reported results demonstrate thatthe functionalization of L-ornithine side-chain with a neutralsulfamoyl group can generate an arginine bioisosterewhich can be used for the synthesis of prototypes of a newclass of human thrombin inhibitors.