Synthesis of an N-3-guanidinopropylglycine (Narg) derivative as a versatile building block for solid-phase peptide and peptoid synthesis.

Abstract

N-(2,2,5,7,8-Pentamethylchroman-6-sulfonyl)-N'-3- (N-9-fluorenylmethoxycarbonyl-glycinyl)propylguanidine (1) was prepared and utilized as an arginine surrogate (Narg) building block compatible with solid-phase synthesis according to the Fmoc methodology. Narg is potentially useful in the assembly of combinatorial compound libraries or in the preparation of modified peptides. The applicability of this building block was demonstrated by its incorporation into an analogue of Thr-Arg-Ser-Ala-Trp, a pentapeptide for which inhibition of osteoclastic bone resorption was claimed. The modified pentapeptide showed an increased proteolytic stability when compared to the original inhibitor.