Simple and Efficient Solution-Phase Synthesis of Oligonucleotides Using Extractive Work-Up

Koning, Martijn C. de; Ghisaidoobe, Amar B. T.; Duynstee, Howard I.; Kortenaar, Paul B. W. Ten; Filippov, and Dmitri V.; Marel, Gijs A. van der

doi:10.1021/op060133q

Cited by 39 publications

(41 citation statements)

References 10 publications

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“…[27,28] As a model compound, the trimer TXG (X = 12) was synthesized in solution according to a recently published procedure. [29] After FPLC purification, MALDI-TOF analysis confirmed the synthesis of the desired compound. The phosphane introduction was carried out with 4 equiv.…”

Section: Resultsmentioning

confidence: 90%

Functionalization of Mono‐ and Oligonucleotides with Phosphane Ligands by Amide Bond Formation

et al. 2010

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Seven phosphane‐functionalized deoxyuridines have been prepared by amide bond formation between aminodeoxyuridines and phosphanylcarboxylic acids. X‐ray crystal structures for two of these new modified nucleosides have been obtained. The same coupling method has been extended to oligonucleotides. The phosphane containing strands have been purified and characterized by MALDI‐TOF and, for the first time, 31P NMR spectrometry. Coordination of a phosphane‐modified 15‐mer to a [PdCl(η3‐allyl)] moiety has been confirmed by 31P NMR spectroscopy.

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Section: Resultsmentioning

confidence: 90%

Functionalization of Mono‐ and Oligonucleotides with Phosphane Ligands by Amide Bond Formation

et al. 2010

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“…Coupling of propanediol amidite 17 and guanosine 8 followed by oxidation of the intermediate phosphite ester gave 18 in good yield. Removal of the DMTr group with methanolic HCl [12] gave 19 in quantitive yield. Instead of using DIA amidite 14 to extend synthon 19 we investigated an alternate approach in which 19 was converted to amidite 20 and then reacted with DIA alcohol 13 .…”

Section: Resultsmentioning

confidence: 99%

“…Using conventional solution phase chemistry, which allows for convergent strategies and more efficient use of valuable intermediates, we have synthesized a group of aza-sugar-containing 2′-O-methyl di, tri and tetra RNA nucleotides that probe both aza-sugar structure and the nucleotide context required for inhibition of SAP [12,13]. Compounds 2–4 were resynthesised for comparison and to provide sufficient material for chemical characterization.…”

Section: Introductionmentioning

confidence: 99%

Oligonucleotide transition state analogues of saporin L3

Mason

Yuan

Evans

et al. 2017

European Journal of Medicinal Chemistry

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Ribosome inactivating proteins (RIPs) are among the most toxic agents known. More than a dozen clinical trials against refractory cancers have been initiated using modified RIPs with impressive results. However, dose-limiting toxicity due to vascular leak syndrome limits success of the therapy. We have previously reported some tight-binding transition state analogues of Saporin L3 that mimic small oligonucleotide substrates in which the susceptible adenosine has been replaced by a 9-deazaadenyl hydroxypyrrolidinol derivative. They provide the first step in the development of rescue agents to prevent Saporin L3 toxicity on non-targeted cells. Here we report the synthesis, using solution phase chemistry, of these and a larger group of transition state analogues. They were tested for inhibition against Saporin L3 giving Ki values as low as 3.3 nM and indicating the structural requirements for inhibition.

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“…Pentaerythritol-based (Kungurtsev et al, 2013;Molina et al, 2015;Molina et al, 2014) 5-mer (20 nucleotides, 4-arm) P (×2) 1.5 eq/branch (DNA/RNA) (Adaman-1-yl)acetyl (de Koning et al, 2006) 6-mer (6 nucleotides, 1-arm) E (×8) 1.5 eq. (DNA)…”

Section: Of 17mentioning

confidence: 99%

Liquid‐Phase Oligonucleotide Synthesis: Past, Present, and Future Predictions

Molina

Sanghvi²

2019

CP Nucleic Acid Chemistry

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Therapeutic oligonucleotides have emerged as a powerful paradigm with the ability to treat a wide range of the human diseases. As a result, we have witnessed more than one hundred oligonucleotides currently in active clinical trials and eight Food and Drug Administration (FDA)‐approved drugs. Until now, the demand for oligonucleotide‐based drugs has been fulfilled by conventional solid‐phase synthesis in an effective manner. However, there are products in advanced stages of clinical trials projecting a collective demand of metric ton quantities in the near future. Therefore, large‐scale manufacturing of these products has become a high priority for process chemists. This article summarizes the advances in liquid‐phase oligonucleotide synthesis (LPOS) as a possible alternative strategy to meet the scale‐up challenge. A review of the literature describing major efforts in developing LPOS technologies is presented. Gratifyingly, serious attempts are under way to develop an efficient environmentally benign green chemistry protocol that is scalable and cost effective for the manufacturing of oligonucleotides. A summary of the most innovative LPOS protocols has been included to provide a glimpse of what may be possible in the future for large‐scale production of oligonucleotides. © 2019 by John Wiley & Sons, Inc.

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Simple and Efficient Solution-Phase Synthesis of Oligonucleotides Using Extractive Work-Up

Cited by 39 publications

References 10 publications

Functionalization of Mono‐ and Oligonucleotides with Phosphane Ligands by Amide Bond Formation

Functionalization of Mono‐ and Oligonucleotides with Phosphane Ligands by Amide Bond Formation

Oligonucleotide transition state analogues of saporin L3

Liquid‐Phase Oligonucleotide Synthesis: Past, Present, and Future Predictions

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