Combined Chemical‐Enzymatic Assembly of Aminoglycoside Derivatives with N‐1‐AHB Side Chain

A series of unprotected pseudo-disaccharides and pseudo-trisaccharides of 2-deoxystreptamine-containing aminoglycosides have been selectively acylated at the N-1 position with the valuable (S)-4-amino-2-hydroxybutanoyl (AHB) pharmacophore by using the recombinant BtrH and BtrG enzymes from butirosin biosynthesis in combination with a synthetic acyl donor. The process was optimized by performing two enzymatic steps in a sequential manner without purification of the intermediate product.

[1]  T. Baasov,et al.  Designer aminoglycosides: the race to develop improved antibiotics and compounds for the treatment of human genetic diseases. , 2008, Organic & biomolecular chemistry.

[2]  E. Westhof,et al.  Crystal Structure of the Bacterial Ribosomal Decoding Site Complexed with a Synthetic Doubly Functionalized Paromomycin Derivative: a New Specific Binding Mode to an A‐Minor Motif Enhances in vitro Antibacterial Activity , 2007, ChemMedChem.

[3]  Z. Ahmed,et al.  In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome , 2007, Human Genetics.

[4]  C. Chang,et al.  Investigation of the regioselectivity for the staudinger reaction and its application for the synthesis of aminoglycosides with N-1 modification. , 2007, The Journal of organic chemistry.

[5]  Li-he Zhang,et al.  Modifications of aminoglycoside antibiotics targeting RNA , 2007, Medicinal research reviews.

[6]  Yanyan Li,et al.  Biosynthesis of butirosin: transfer and deprotection of the unique amino acid side chain. , 2007, Chemistry & biology.

[7]  E. Selimoğlu,et al.  Aminoglycoside-induced ototoxicity. , 2007, Current pharmaceutical design.

[8]  T. Baasov,et al.  Redesign of aminoglycosides for treatment of human genetic diseases caused by premature stop mutations. , 2006, Bioorganic & medicinal chemistry letters.

[9]  E. Westhof,et al.  Crystal structure of the bacterial ribosomal decoding site complexed with amikacin containing the γ-amino-α-hydroxybutyryl (haba) group , 2006 .

[10]  C. Chang,et al.  Recent Developments in the Synthesis of Novel Aminoglycoside Antibiotics , 2006 .

[11]  Ravi Rai,et al.  Design and synthesis of pyrankacin: a pyranmycin class of broad-spectrum aminoglycoside antibiotic. , 2006, Organic letters.

[12]  Samy O Meroueh,et al.  Interactions of designer antibiotics and the bacterial ribosomal aminoacyl-tRNA site. , 2006, Chemistry & biology.

[13]  J. Blanchard,et al.  Molecular insights into aminoglycoside action and resistance. , 2005, Chemical reviews.

[14]  E. Kerem.  Pharmacologic therapy for stop mutations: how much CFTR activity is enough? , 2004, Current opinion in pulmonary medicine.

[15]  Chi‐Huey Wong,et al.  Dimeric aminoglycosides as antibiotics. , 2004, Angewandte Chemie.

[16]  E. Westhof,et al.  Molecular recognition of aminoglycoside antibiotics by ribosomal RNA and resistance enzymes: an analysis of x-ray crystal structures. , 2003, Biopolymers.

[17]  J. Murray,et al.  The complex of a designer antibiotic with a model aminoacyl site of the 30S ribosomal subunit revealed by X-ray crystallography. , 2003, Journal of the American Chemical Society.

[18]  Lakshmi P Kotra,et al.  Design of novel antibiotics that bind to the ribosomal acyltransfer site. , 2002, Journal of the American Chemical Society.

[19]  So Ha Lee,et al.  Selective Reactions of Reactive Amino Groups in Polyamino Compounds by Metal-Chelated or -Mediated Methods , 2001 .

[20]  D. Bedwell,et al.  Aminoglycoside antibiotics mediate context-dependent suppression of termination codons in a mammalian translation system. , 2000, RNA.

[21]  R. Kaufman,et al.  Correction of genetic disease by making sense from nonsense. , 1999, The Journal of clinical investigation.

[22]  Chi‐Huey Wong,et al.  Design and Synthesis of New Aminoglycoside Antibiotics Containing Neamine as an Optimal Core Structure: Correlation of Antibiotic Activity with in Vitro Inhibition of Translation , 1999 .

[23]  K. Hotta,et al.  Semisynthetic aminoglycoside antibiotics: Development and enzymatic modifications , 1999, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[24]  P. Kelly,et al.  Release factor RF-3 GTPase activity acts in disassembly of the ribosome termination complex. , 1998, RNA.

[25]  J. F. Atkins,et al.  A dual-luciferase reporter system for studying recoding signals. , 1998, RNA.

[26]  G. Wright,et al.  Aminoglycoside antibiotics. Structures, functions, and resistance. , 1998, Advances in experimental medicine and biology.

[27]  J. Burke,et al.  Suppression of a nonsense mutation in mammalian cells in vivo by the aminoglycoside antibiotics G-418 and paromomycin. , 1985, Nucleic acids research.

[28]  H. Kirst,et al.  Control of site-specific substitution of aminoglycosides by transition metal cations , 1981 .

[29]  H. Kawaguchi,et al.  Aminoglycoside antibiotics. VII. Acute toxicity of aminoglycoside antibiotics. , 1974, The Journal of antibiotics.

[30]  H. Umezawa,et al.  SYNTHESES OF (S)-4-AMINO-2-HYDROXYBUTYRYL DERIVATIVES OF 3', 4'-DIDEOXYKANAMYCIN B AND THEIR ANTIBACTERIAL ACTIVITIES , 1973 .

[31]  H. Umezawa,et al.  Letter: Syntheses of 1-n-(S)-4-amino-2-hydroxybutyryl)-kanamycin B and -3', 4'-dideoxykanamycin B active against kanamycin-resistant bacteria. , 1973, The Journal of antibiotics.

[32]  H. Kawaguchi,et al.  BB-K 8, a new semisynthetic aminoglycoside antibiotic. , 1972, The Journal of antibiotics.

[33]  H. Umezawa,et al.  Synthesis of butirosin B. , 1972, The Journal of antibiotics.

[34]  L. Anderson,et al.  Butirosin, a New Aminoglycosidic Antibiotic Complex: Bacterial Origin and Some Microbiological Studies , 1972, Antimicrobial Agents and Chemotherapy.