The Future of Aminoglycosides: The End or Renaissance?

被引:150
作者
Houghton, Jacob L. [1 ,3 ]
Green, Keith D. [3 ]
Chen, Wenjing [2 ,3 ]
Garneau-Tsodikova, Sylvie [1 ,2 ,3 ]
机构
[1] Univ Michigan, Coll Pharm, Dept Med Chem, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Chem Biol Doctoral Program, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA
关键词
aminoglycosides; antibiotics; antiviral agents; chemoenzymatic synthesis; drug resistance; genetic diseases; GCN5-RELATED N-ACETYLTRANSFERASE; ANTIBIOTIC-RESISTANCE ENZYME; DIMERIZATION INITIATION SITE; 30S RIBOSOMAL-SUBUNIT; CRYSTAL-STRUCTURE; A-SITE; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; SUBSTRATE-SPECIFICITY; MODIFYING ENZYME;
D O I
10.1002/cbic.200900779
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Although aminoglycosides have been used as antibacterials for decades, their use has been hindered by their inherent toxicity and the resistance that has emerged to these compounds. It seems that such issues have relegated a formerly front-line class of antimicrobials to the proverbial back shelf. However, recent advances have demonstrated that novel aminoglycosides have a potential to overcome resistance as well as to be used to treat HIV-1 and even human genetic disorders, with abrogated toxicity. It is not the end for aminoglycosides, but rather, the challenges faced by researchers have led to ingenuity and a change in how we view this class of compounds, a renaissance.
引用
收藏
页码:880 / 902
页数:23
相关论文
共 167 条
[141]   Versatility of Aminoglycosides and prospects for their future [J].
Vakulenko, SB ;
Mobashery, S .
CLINICAL MICROBIOLOGY REVIEWS, 2003, 16 (03) :430-+
[142]   Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1 [J].
Venkataraman, Nitya ;
Cole, Amy L. ;
Ruchala, Piotr ;
Waring, Alan J. ;
Lehrer, Robert I. ;
Stuchlik, Olga ;
Pohl, Jan ;
Cole, Alexander M. .
PLOS BIOLOGY, 2009, 7 (04) :720-729
[143]   Mechanistic and structural analysis of aminoglycoside N-acetyltransferase AAC(6′)-Ib and its bifunctional, fluoroquinolone-active AAC(6′)-Ib-cr variant [J].
Vetting, Matthew W. ;
Park, Chi Hye ;
Hegde, Subray S. ;
Jacoby, George A. ;
Hooper, David C. ;
Blanchard, John S. .
BIOCHEMISTRY, 2008, 47 (37) :9825-9835
[144]   A bacterial acetyltransferase capable of regioselective N-acetylation of antibiotics and histones [J].
Vetting, MW ;
Magnet, S ;
Nieves, E ;
Roderick, SL ;
Blanchard, JS .
CHEMISTRY & BIOLOGY, 2004, 11 (04) :565-573
[145]   Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates [J].
Vetting, MW ;
Hegde, SS ;
Javid-Majd, F ;
Blanchard, JS ;
Roderick, SL .
NATURE STRUCTURAL BIOLOGY, 2002, 9 (09) :653-658
[146]   Crystal structure of geneticin bound to a bacterial 16 S ribosomal RNA A site oligonucleotide [J].
Vicens, Q ;
Westhof, E .
JOURNAL OF MOLECULAR BIOLOGY, 2003, 326 (04) :1175-1188
[147]   Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: An analysis of x-ray crystal structures [J].
Vicens, Q ;
Westhof, E .
BIOPOLYMERS, 2003, 70 (01) :42-57
[148]   Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site [J].
Vicens, Q ;
Westhof, E .
CHEMISTRY & BIOLOGY, 2002, 9 (06) :747-755
[149]   Crystal structure of paromomycin docked into the eubacterial ribosomal decoding a site [J].
Vicens, Q ;
Westhof, E .
STRUCTURE, 2001, 9 (08) :647-658
[150]   Aminoglycoside-hybrid ligands targeting the ribosomal decoding site [J].
Vourloumis, D ;
Winters, GC ;
Simonsen, KB ;
Takahashi, M ;
Ayida, BK ;
Shandrick, S ;
Zhao, Q ;
Han, Q ;
Hermann, T .
CHEMBIOCHEM, 2005, 6 (01) :58-65