2-Deoxystreptamine:  Central Scaffold of Aminoglycoside Antibiotics

Busscher, Guuske F.; Rutjes, Floris P. J. T.; Delft, Floris L. van

doi:10.1021/cr0404085

Cited by 136 publications

(76 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, streptothricin is found in some 10% of all streptomycetes isolated randomly from soil and streptomycin is found in 1% and actinomycin in 0.1%, while conversely, erythromycin and vancomycin are found in around 10 Ϫ5 soil isolates, and daptomycin is found only at a frequency of around 10 Ϫ7 (412). Major classes of clinical antibiotics produced by actinomycetes are the following: aminoglycosides (neomycin, kanamycin, streptomycin (413)(414)(415), angucyclines (auricin; also, antitumor agents like landomycin and moromycin (416), ansamycins (rifamycin, geldanamycin) (417), anthracyclines (primarily antitumor agents, e.g., daunorubicin) (418,419), ␤-lactams (cephamycins) (420) and also the important ␤-lactamase inhibitor clavulanic acid (421,422), chloramphenicol (423), glutarimides (cycloheximide) (424), glycopeptides (vancomycin, teichoplanin) (425,426), lipopeptides (daptomycin) (427), lantibiotics (mersacidin, actagardine) (272), macrolides (clarythromycin, erythromycin, tylosin, clarithromycin) (428,429), oxazolidinones (cycloserine) (430), streptogramins (streptogramin) (431), and tetracyclines (432). The producing capacity of individual actinomycetes can also vary enormously.…”

Section: Actinobacteria As Sources Of Antibioticsmentioning

confidence: 99%

Taxonomy, Physiology, and Natural Products of Actinobacteria

Barka

Vatsa

Sanchez

et al. 2016

Microbiol Mol Biol Rev

1,600

1,048

View full text Add to dashboard Cite

SUMMARYActinobacteriaare Gram-positive bacteria with high G+C DNA content that constitute one of the largest bacterial phyla, and they are ubiquitously distributed in both aquatic and terrestrial ecosystems. ManyActinobacteriahave a mycelial lifestyle and undergo complex morphological differentiation. They also have an extensive secondary metabolism and produce about two-thirds of all naturally derived antibiotics in current clinical use, as well as many anticancer, anthelmintic, and antifungal compounds. Consequently, these bacteria are of major importance for biotechnology, medicine, and agriculture.Actinobacteriaplay diverse roles in their associations with various higher organisms, since their members have adopted different lifestyles, and the phylum includes pathogens (notably, species ofCorynebacterium,Mycobacterium,Nocardia,Propionibacterium, andTropheryma), soil inhabitants (e.g.,MicromonosporaandStreptomycesspecies), plant commensals (e.g.,Frankiaspp.), and gastrointestinal commensals (Bifidobacteriumspp.).Actinobacteriaalso play an important role as symbionts and as pathogens in plant-associated microbial communities. This review presents an update on the biology of this important bacterial phylum.

show abstract

Section: Actinobacteria As Sources Of Antibioticsmentioning

confidence: 99%

Taxonomy, Physiology, and Natural Products of Actinobacteria

Barka

Vatsa

Sanchez

et al. 2016

Microbiol Mol Biol Rev

1,600

1,048

View full text Add to dashboard Cite

show abstract

“…The binding mode of this class of antibiotics relies on multiple hydrogen bonds and electrostatic interactions, which require the participation of basic functional groups distributed on the flexible 2-deoxystreptamine scaffold [10,71,72]. The presence of six amino groups in NB versus only five in TB and PR (Scheme 2) was considered responsible for the lower dissociation constant determined in solution for NB·SL3 (i.e., 4.2 Ϯ 0.3 M) than for the other two complexes (i.e., 38.7 Ϯ 3.7 M and 37.7 Ϯ 1.3 M, respectively) [12].…”

Section: G G a C U A G C G G A G G C U A G U C Cmentioning

confidence: 99%

Mapping noncovalent ligand binding to stemloop domains of the HIV-1 packaging signal by tandem mass spectrometry

Turner

Hagan

Kohlway

et al. 2006

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

The binding modes and structural determinants of the noncovalent complexes formed by aminoglycoside antibiotics with conserved domains of the HIV-1 packaging signal (⌿-RNA) were investigated using electrospray ionization (ESI) Fourier transform mass spectrometry (FTMS). The location of the aminoglycoside binding sites on the different stemloop structures was revealed by characteristic coverage gaps in the ion series obtained by sustained off-resonance irradiation collision induced dissociation (SORI-CID) of the antibiotic-RNA assemblies. The site positions were confirmed using mutants that eliminated salient structural features of the ⌿-RNA domains. The effects of the mutations on the binding properties of the different substrates served to validate the position of the aminoglycoside site on the wild-type structures. Additional information was provided by docking experiments performed on the different aminoglycoside-stemloop complexes. The results have shown that, in the absence of features disrupting the regular A-helix of the double-stranded stem, aminoglycosides tend to bind in an area situated between the upper stem and the loop regions, as demonstrated for stemloop SL3. The presence of a tandem wobbles motif in SL4 modifies the regular geometry of the upper stem, which does not affect the general site location, but greatly increases its solution binding affinity compared with SL3. The platform motif in SL2 locates the binding site in the stem midsection and confers upon this stemloop an intermediate affinity toward aminoglycosides. In SL3 and SL4, the extensive overlap of the antibiotic site with the region used to bind the nucleocapsid (NC) protein provides the basis for a competition mechanism that could explain the aminoglycoside inhibition of the NC·SL3 and NC·SL4 assemblies. In contrast, the minimal overlap between the aminoglycoside and the NC sites in SL2 accounts for the absence of inhibition of the NC·SL2 complex. . The relatively low mutation frequency of this ϳ120 nt stretch of genomic RNA makes the packaging signal a very promising target for the development of new therapeutic strategies to contend with the rapid emergence of drug resistant strains [7,8]. For this reason, steps have been made toward the identification of possible inhibitors that may bind specific ⌿-RNA structures and disrupt their normal functions [9 -11]. In a systematic investigation of classic nucleic acid ligands, we have recently shown that aminoglycosidic antibiotics are not only capable of binding individual domains of ⌿-RNA, but can also inhibit their interactions with NC in a structure-specific fashion [12]. Initial tests to locate the actual binding sites on the different RNA substrates, which is crucial to explain the mechanism of preferential inhibition, were based on the analysis of mutant-ligand complexes performed by electrospray ionization (ESI) [13,14] and Fourier transform mass spectrometry (FTMS) [15,16].The favorable energetics characteristic of ESI enable the analysis of relatively labile noncovalent complex...

show abstract

“…4 This motif plays a crucial role in RNA recognition and biological activity. Therefore, mimicking the 2-DOS structure has been of great interest in preparing novel aminoglycoside analogs.…”

Section: Introductionmentioning

confidence: 99%

Epoxide ring-opening approach to the synthesis of diverse trisubstituted cyclopentanes

Larin¹,

Atroshchenko²

2016

Arkivoc

View full text Add to dashboard Cite

The regiospecificity of the epoxide ring-opening reactions of (1RS,2SR,3SR)-1,2-epoxy-3-(Nbenzyl-N-methylamino)-cyclopentane 1 and (1RS,2SR,3SR)-1,2-epoxy-3-(N,N-dibenzylamino)-cyclopentane 2 with O-and C-nucleophiles has been explored. It has been shown that electronic and steric factors could affect the regioisomeric ratio of the products due to the possibility for a nucleophile to attack both oxirane carbon atoms. New mimics of 2-deoxystreptamine (2-DOS), the main structural motif of aminoglycoside type antibiotics, have been synthesized.

show abstract

2-Deoxystreptamine: Central Scaffold of Aminoglycoside Antibiotics

Cited by 136 publications

References 112 publications

Taxonomy, Physiology, and Natural Products of Actinobacteria

Taxonomy, Physiology, and Natural Products of Actinobacteria

Mapping noncovalent ligand binding to stemloop domains of the HIV-1 packaging signal by tandem mass spectrometry

Epoxide ring-opening approach to the synthesis of diverse trisubstituted cyclopentanes

Contact Info

Product

Resources

About