Synthesis of glucose-templated lysine analogs and incorporation into the antimicrobial dipeptide sequence kW-OBn.
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.
Zhang
Kaidong
K
Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
Mondal
Dhananjoy
D
Zhanel
George G
GG
Schweizer
Frank
F
D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D005947:Glucose / Q000031:analogs & derivatives / Q000138:chemical synthesis; D008239:Lysine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism
D004151:Dipeptides; D005947:Glucose; D008239:Lysine