The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity

Xuxu Yan; Feng Gao; Sirilata Yotphan; Parseh Bakirtzian; Karine Auclair

doi:10.1016/j.bmc.2007.02.009

The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH₂ in antibacterial activity

Xuxu Yan
, Feng Gao
, Sirilata Yotphan
, Parseh Bakirtzian
, Karine Auclair

McGill University

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding between 6′-NH₂ and 16S rRNA for antibacterial activity.

Original language	English
Pages (from-to)	2944-2951
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	15
Issue number	8
DOIs	https://doi.org/10.1016/j.bmc.2007.02.009
Publication status	Published - 15 Apr 2007
Externally published	Yes

Keywords

A-site
Acetyltransferase
Aminoglycoside
Antibacterial
Antibiotic
Neamine
RNA
Regioselective
Resistance

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10.1016/j.bmc.2007.02.009

Cite this

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title = "The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity",

abstract = "Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding between 6′-NH2 and 16S rRNA for antibacterial activity.",

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author = "Xuxu Yan and Feng Gao and Sirilata Yotphan and Parseh Bakirtzian and Karine Auclair",

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TY - JOUR

T1 - The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH2 in antibacterial activity

AU - Yan, Xuxu

AU - Gao, Feng

AU - Yotphan, Sirilata

AU - Bakirtzian, Parseh

AU - Auclair, Karine

PY - 2007/4/15

Y1 - 2007/4/15

N2 - Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding between 6′-NH2 and 16S rRNA for antibacterial activity.

AB - Aminoglycoside antibiotics act by binding to 16S rRNA. Resistance to these antibiotics occurs via drug modifications by enzymes such as aminoglycoside 6′-N-acetyltransferases (AAC(6′)s). We report here the regioselective and efficient synthesis of N-6′-acylated aminoglycosides and their use as probes to study AAC(6′)-Ii and aminoglycoside-RNA complexes. Our results emphasize the central role of N-6′ nucleophilicity for transformation by AAC(6′)-Ii and the importance of hydrogen bonding between 6′-NH2 and 16S rRNA for antibacterial activity.

KW - A-site

KW - Acetyltransferase

KW - Aminoglycoside

KW - Antibacterial

KW - Antibiotic

KW - Neamine

KW - RNA

KW - Regioselective

KW - Resistance

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U2 - 10.1016/j.bmc.2007.02.009

DO - 10.1016/j.bmc.2007.02.009

M3 - Article

C2 - 17317190

AN - SCOPUS:33947176697

SN - 0968-0896

VL - 15

SP - 2944

EP - 2951

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 8

ER -

The use of aminoglycoside derivatives to study the mechanism of aminoglycoside 6′-N-acetyltransferase and the role of 6′-NH₂ in antibacterial activity

Abstract

Keywords

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