Oligonucleotides with a nuclease-resistant sulfur-based linkage

Huie, Edward M.; Kirshenbaum, M. R.; Trainor, George L.

doi:10.1021/jo00043a004

Cited by 42 publications

(21 citation statements)

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“…The targeted sequence being very specific, it required the synthesis of the SUL-d(GA) dimer. 354 The synthesis started with the reduction of 5 0 -azido-N 6 -benzoyl-2 0 ,5 0 -dideoxyadenosine (120) using a H 2 and Pd/C catalytic system. The sulfamoylazide derivative 121 was obtained by reaction with chlorosulfonyl azide.…”

Section: Rsc Chemical Biology Reviewmentioning

confidence: 99%

Modified internucleoside linkages for nuclease-resistant oligonucleotides

et al. 2021

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Section: Rsc Chemical Biology Reviewmentioning

confidence: 99%

Modified internucleoside linkages for nuclease-resistant oligonucleotides

et al. 2021

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“…A number of modifications have been introduced involving replacing the PO 2group of native oligos with neutral isosteric and isoelectronic SO 2 groups. These include dimethylene sulfones 50 [25,127], sulfonamides 51 [128], sulfonates 52 [129], 5´-N-sulfamates 53 [130], 3´-Nsulfamates 54 [131] and sulfamides 55 [132] (Fig. 16).…”

Section: Backbones Containing Sulfonyl Groupsmentioning

confidence: 99%

“…-5 ˚C ∆T m /mod) [128], which suggest that these modifications will not be useful in antisense or antigene experiments. An early paper on 5´-N-sulfamates 53, reports the incorporation of one sulfamate linkage into each of two complementary mixed sequence DNA 20mers, resulting a drop in T m of -1.5 ˚C per modification [130]. Despite this no further reports have been published.…”

Section: Backbones Containing Sulfonyl Groupsmentioning

confidence: 99%

Backbone Modification of Nucleic Acids: Synthesis, Structure and Therapeutic Applications

Micklefield

2001

CMC

180

118

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Nucleic acids have been extensively modified by replacing the phosphodiester group or the whole sugar phosphodiester with alternative anionic, neutral and cationic structures. Several of these modified oligonucleotides exhibit improved properties including enhanced recognition and binding to RNA, duplex DNA and proteins. This has resulted in the development of new and more potent antisense and antigene agents, as well as aptamers. Furthermore, backbone modified oligonucleotides have also been used in the development of several alternative strategies, which rely on altogether different mechanisms of action and show significant promise for therapeutic intervention. In this review the latest advances in the synthesis and evaluation of the most promising backbone modified oligos will be discussed, with a view to their future as novel pharmaceuticals.

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“…The crude 5′-aminonucleosides were then transformed to the 5′-sulfamides 43a – f in 84–94% yield by refluxing with sulfamide (NH 2 SO 2 NH 2 ) in 1,4-dioxane for 2 h. This new method of sulfamide synthesis is superior to previous examples in terms of yield and experimental simplicity. 4c, 29 The synthesis of the target molecules was completed by salicylation of sulfamides 43a – f with NHS-ester 44 to obtain fully protected coupled products 45a–f and global deprotection furnished 7–12 in 39–50% yield. 30 …”

Section: Resultsmentioning

confidence: 99%

Investigation and Conformational Analysis of Fluorinated Nucleoside Antibiotics Targeting Siderophore Biosynthesis

et al. 2015

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Antibiotic resistance represents one of the greatest threats to public health. The adenylation inhibitor 5′-O-[N-(salicyl)sulfamoyl]adenosine (SAL-AMS) is the archetype for a new class of nucleoside antibiotics that target iron acquisition in pathogenic microorganisms and is especially effective against Mycobacterium tuberculosis, the causative agent of tuberculosis. Strategic incorporation of fluorine at the 2′ and 3′ positions of the nucleoside was performed by direct fluorination to enhance activity and improve drug disposition properties. The resulting SAL-AMS analogs were comprehensively assessed for biochemical potency, whole-cell antitubercular activity, and in vivo pharmacokinetic parameters. Conformational analysis suggested a strong preference of fluorinated sugar rings for either a 2'-endo, 3'-exo (South) or a 3'-endo, 2'-exo (North) conformation. The structure–activity relationships revealed a strong conformational bias for the C3′-endo conformation to maintain potent biochemical and whole-cell activity whereas improved pharmacokinetic properties were associated with the C2′-endo conformation.

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Oligonucleotides with a nuclease-resistant sulfur-based linkage

Cited by 42 publications

References 0 publications

Modified internucleoside linkages for nuclease-resistant oligonucleotides

Modified internucleoside linkages for nuclease-resistant oligonucleotides

Backbone Modification of Nucleic Acids: Synthesis, Structure and Therapeutic Applications

Investigation and Conformational Analysis of Fluorinated Nucleoside Antibiotics Targeting Siderophore Biosynthesis

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