Synthesis of glucose-templated lysine analogs and incorporation into the antimicrobial dipeptide sequence kW-OBn

Carbohydr Res. 2008 Jul 21;343(10-11):1644-52. doi: 10.1016/j.carres.2008.04.018. Epub 2008 Apr 22.

Abstract

The synthesis of two glucose-templated (GlcT) lysine analogs GlcTK and GlcTk in which the side chain of D- and L-lysine (k and K) is conformationally constrained via incorporation into a D-glucose scaffold is described. A key-step in the synthesis is a high yielding, reductive ring opening of an exocyclic glucose-derived epoxide to form a alpha-hydroxy ester that can be converted into GlcTK and GlcTk. To demonstrate the use of these building blocks in peptide synthesis, we replaced D-lysine in the antimicrobial dipeptide sequence kW-OBn (W=L-tryptophan) and determined the antibacterial activity against various gram-positive and gram-negative organisms. Our results show that the replacement of D-lysine by unprotected GlcTk in dipeptide kW-OBn results in reduced antibacterial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dipeptides / chemical synthesis*
  • Dipeptides / pharmacology
  • Glucose / analogs & derivatives
  • Glucose / chemical synthesis
  • Lysine / analogs & derivatives*
  • Lysine / chemical synthesis
  • Microbial Sensitivity Tests
  • Stereoisomerism

Substances

  • Dipeptides
  • Glucose
  • Lysine