6-hydroxy to 6'''-amino tethered ring-to-ring macrocyclic aminoglycosides as probes for APH(3')-IIIa kinase.
Based on molecular modeling and available X-ray structure data on aminoglycosides complexed with a bacterial ribosomal surrogate or with a kinase, two analogues of paromomycin were prepared by tethering the 6-OH and the 6'''-NH(2) group with a five-carbon bridge. Only one of two possible hydroxyl groups was phosphorylated by the kinase. The application of ring closure metathesis is presented for the first time to construct bridged macrocyclic analogues in the aminoglycoside series.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succ. Centre-Ville, Montréal, P.Q., Canada H3C 3J7. stephen.hanessian@umontreal.ca
Szychowski
Janek
J
Campos-Reales Pineda
Natalhie B
NB
Furtos
Alexandra
A
Keillor
Jeffrey W
JW
D000617:Aminoglycosides / Q000737:chemistry* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D019868:Kanamycin Kinase / Q000737:chemistry*; D008958:Models, Molecular; D015335:Molecular Probes / Q000737:chemistry*; D015394:Molecular Structure; D013211:Staphylococcus aureus / Q000187:drug effects
D000617:Aminoglycosides; D015335:Molecular Probes; D019868:Kanamycin Kinase