A practical synthesis of gramicidin s and sugar amino Acid containing analogues

Gijsbert M Grotenbreg; Martijn Kronemeijer; Mattie S M Timmer; Farid El Oualid; Renate M van Well; Martijn Verdoes; Emile Spalburg; Peter A V van Hooft; Albert J de Neeling; Daan Noort; Jacques H van Boom; Gijsbert A van der Marel; Herman S Overkleeft; Mark Overhand

doi:10.1021/jo0487449

A practical synthesis of gramicidin s and sugar amino Acid containing analogues

J Org Chem. 2004 Nov 12;69(23):7851-9. doi: 10.1021/jo0487449.

Authors

Gijsbert M Grotenbreg¹, Martijn Kronemeijer, Mattie S M Timmer, Farid El Oualid, Renate M van Well, Martijn Verdoes, Emile Spalburg, Peter A V van Hooft, Albert J de Neeling, Daan Noort, Jacques H van Boom, Gijsbert A van der Marel, Herman S Overkleeft, Mark Overhand

Affiliation

¹ Leiden Institute of Chemistry, Gorlaeus Laboratories, P.O. Box 9502, 2300 RA Leiden, The Netherlands.

PMID: 15527261
DOI: 10.1021/jo0487449

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acids / chemical synthesis*
Amino Acids / pharmacology
Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / pharmacology
Bacillus cereus / drug effects
Carbohydrates / chemical synthesis*
Carbohydrates / pharmacology
Enterococcus faecalis / drug effects
Erythrocytes / drug effects
Escherichia coli / drug effects
Gramicidin / chemical synthesis*
Gramicidin / pharmacology
Humans
Microbial Sensitivity Tests
Staphylococcus / drug effects

Substances

Amino Acids
Anti-Bacterial Agents
Carbohydrates
Gramicidin