Grotenbreg Gijsbert M, Kronemeijer Martijn, Timmer Mattie S M, El Oualid Farid, van Well Renate M, Verdoes Martijn, Spalburg Emile, van Hooft Peter A V, de Neeling Albert J, Noort Daan, van Boom Jacques H, van der Marel Gijsbert A, Overkleeft Herman S, Overhand Mark
Leiden Institute of Chemistry, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
J Org Chem. 2004 Nov 12;69(23):7851-9. doi: 10.1021/jo0487449.
A practical gram-scale and high-yielding synthesis of the antimicrobial peptide gramicidin S is presented. An Fmoc-based solid-phase peptide synthesis protocol is employed for the generation of the linear decapeptide precursor, which is cyclized in solution to afford the target compound. The versatility of our method is demonstrated by the construction of eight gramicidin S analogues (15a-h) having nonproteinogenic sugar amino acid residues (4-7) incorporated in the turn regions.
