【摘要】 氨基糖苷类抗生素是高效、广谱的杀菌药物。随着在临床的广泛应用,抗生素的抗药性日趋严重,这在很大程度上降低了其临床应用的潜力。其中,最主要的原因就是细菌产生了一系列修饰酶修饰抗生素的特定基团,使其失去药效。细菌产生的修饰酶种类众多,主要包括磷酸化、乙酰化和腺苷化修饰酶。研究发现,一种酶可以修饰多种抗生素,同时,一种抗生素也可以被多种修饰酶修饰。由于修饰酶底物的广谱性,使得细菌的耐药性难以克服。因此,本文就氨基糖苷类修饰酶和抗生素相互作用的热力学和动力学性质进行了详细的论述,试图找出不同修饰酶失活抗生素药物的共同作用机制。这将为设计新的抗生素药物及修饰酶抑制剂、克服细菌的耐药性,提供理论指导和技术支持。更多还原

【Abstract】 Aminoglycosides are valuable and broad spectrum of bactericidal antibiotics.However,their therapeutic effectiveness has been severely reduced in recent decades due to the emergence of bacterial strains that are insensitive to aminoglycoside action.The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme-catalysed chemical modification on the special groups of the drug.Aminoglycoside-modifying enzymes are widely distributed among bacterial pathogens and include O-phosphoryltransferases(kinases),N-acetyltransferases,and O-adenyltransferases.These enzymes can use several aminoglycosides as substrates regardless of size and structural differences among them.Conversely,each aminoglycoside can be a substrate for many different AGMEs.In this review,the authors describe the thermodynamic characterization of aminoglycoside modified enzyme interacted with antibiotics in an effort to define shared aspects of enzyme-aminoglycoside complexes,which provides the necessary tools and understanding to design new drugs to combat antibiotic resistance.更多还原