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′-NH 2 and 16S rRNA for antibacterial activity.
While prenatal environmental tobacco smoke (ETS) exposure is a well-known risk factor for sudden infant death syndrome, the effect of postnatal ETS exposure is less clear.The objective of this study was to investigate the effect of postnatal ETS exposure on non-nutritive swallowing (NNS) and NNS-breathing coordination. Twelve newborn lambs were exposed to either ten or twenty cigarettes per day for 15 days. Six controls were exposed to air. Lambs were instrumented for recording states of alertness, swallowing, electrocardiogram and breathing; recordings were performed in non-sedated lambs at the end of ETS exposure. Urinary cotinine/creatinine ratio confirmed relevant real-life exposure. Postnatal ETS exposure had no effect on NNS frequency but tended to decrease inspiratory NNS (p = 0.07) during quiet sleep. No effect on respiratory or heart rate (p > 0.6), apnea index (p = 0.2) or sleep states (p = 0.3) was observed. In conclusion, postnatal ETS exposure in lambs had only mild effects on NNS-breathing coordination.
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