N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin antibiotics.
The synthesis and the biological properties of a series of N15-alkyl and N15,N15-dialkyl derivatives of teicoplanin A2, its pseudoaglycones and aglycone are described. The alkylation of the terminal amino group did not affect the ability of these teicoplanin derivatives to bind with Ac2-L-Lys-D-Ala-D-Ala, a synthetic model of the antibiotic's target peptide in bacterial cell walls, but influenced their in vitro and in vivo antimicrobial activities to a different extent, depending on the structure and length of the alkyl chains and the type and number of sugars present.
Malabarba
A
A
Merrell Dow Research Institute, Lepetit Research Center, Varese, Italy.
Trani
A
A
Kettenring
J
J
Gerli
E
E
Pallanza
R
R
Berti
M
M
Cavalleri
B
B
D000478:Alkylation; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy; D013290:Streptococcal Infections / Q000188:drug therapy; D013297:Streptococcus pyogenes / Q000187:drug effects; D017334:Teicoplanin
D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D010455:Peptides; D017334:Teicoplanin