A convenient synthetic pathway for multivalent assembly of aminoglycoside antibiotics starting from amikacin.
Vinylpolymers carrying a kanamycin cluster at the side chain were prepared via regioselective N-acylation of amikacin with N-succinimidyl p-vinylbenzoate, followed by radical homo- and co-polymerization with acrylamide. Two independent biological assays disclosed that the polyvalent kanamycin models showed neither antibacterial activity nor inhibitory activity against rRNA-based protein synthesis, suggesting that the multivalency-binding approach is not valid for integrating the potential of aminoglyoside anitibiotics.
Tanaka
Hidehiko
H
Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University, Chikusa-ku, Nagoya 464-8603, Japan.
Nishida
Yoshihiro
Y
Furuta
Yousuke
Y
Kobayashi
Kazukiyo
K
D000583:Amikacin / Q000031:analogs & derivatives / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001665:Binding Sites; D002473:Cell Wall / Q000187:drug effects; D007612:Kanamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008826:Microbial Sensitivity Tests; D012335:RNA, Ribosomal / Q000737:chemistry; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry; D020058:Styrene / Q000737:chemistry
D000900:Anti-Bacterial Agents; D008024:Ligands; D012335:RNA, Ribosomal; D012269:Ribosomal Proteins; C056045:1-N-(3-amino-2-hydroxybutanoyl)-2',3'-dideoxykanamycin A; D020058:Styrene; D007612:Kanamycin; D000583:Amikacin