Conjugation Reactions Involving Maleimides and Phosphorothioate Oligonucleotides

Sánchez, Albert Ferrer; Pedroso, Enrique; Grandas, Anna

doi:10.1021/bc200598g

Cited by 19 publications

(19 citation statements)

References 36 publications

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“…The [protected maleimido]-oligonucleotides (8 and 11) obtained after reaction with ammonia at room temperature were purified by HPLC ( Figure 2) and characterized by mass spectrometry. Maleimide deprotection was carried out using the method that 60 had performed better in our previous work (12,14), namely heating a suspension of the oligonucleotide in anh. toluene at 90 o C for 4 h. Maleimide deprotection yields were above 90 %, as assessed by HPLC analysis of the crudes (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

2012

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5[2,5-dimethylfuran]-protected maleimides were placed at both internal positions and the 3'-end of oligonucleotides making use of solid-phase synthesis procedures. A new phosphoramidite derivative and a new solid support incorporating the protected maleimide moiety were prepared for this purpose. In all cases maleimide deprotection (retro-Diels-Alder reaction) followed by reaction with thiol-containing compounds afforded the target conjugate.

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Section: Resultsmentioning

confidence: 99%

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

2012

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“…From a chemistry perspective, the sulfur atom in the PS group is more reactive than the oxygen atom in PO group, which provides a nucleophilic site that is amenable to be reacted with electrophilic reagents, such as alkyl halides, bromoacetic compounds, and aziridinylsulfonamide . For instance, phosphorothioated oligonucleotides, including strands with phosphorothioate monoester at the terminus or phosphorothioate diester on the backbone, have been employed to conjugate with functional moieties, such as fluorescent dyes, antibiotics, peptides, and proteins . In general, terminal PS monoester is more active than PS diester, which can even react with maleimide compounds .…”

Section: Methodsmentioning

confidence: 99%

Stressing the Role of DNA as a Drug Carrier: Synthesis of DNA–Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides

et al. 2019

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To stress the role of deoxyribonucleic acid (DNA) as a drug carrier, an efficient conjugation strategy in which chemotherapeutics can be grafted onto a phosphorothiolated DNA backbone through the reaction between the phosphorothioate group (PS) and a benzyl bromide group is proposed. As a proof of concept, benzyl‐bromide‐modified paclitaxel (PTX) is employed to graft onto the DNA backbone at the PS modification sites. Due to the easy preparation of phosphorothiolated DNA at any desired position during its solid‐phase synthesis, diblock DNA strands containing both normal phosphodiester segment (PODNA) and phosphorothiolate segment (PSDNA) are directly grafted with a multitude of PTXs without using complicated and exogenous linkers. Then, the resulting amphiphilic PODNA‐blocked‐(PSDNA‐grafted PTX) conjugates (PODNA‐b‐(PSDNA‐g‐PTX)) assemble into PTX‐loaded spherical nucleic acid (SNA)‐like micellar nanoparticles (PTX‐SNAs) with a high drug loading ratio up to ≈53%. Importantly, the PODNA segment maintains its molecular recognition property and biological functions, which allows the as‐prepared PTX‐SNAs to be further functionalized with tumor‐targeting aptamers, fluorescent probe strands, or antisense sequences. These multifunctional PTX‐SNAs demonstrate active tumor‐targeting delivery, efficient inhibition of tumor growth, and the reversal of drug resistance both in vitro and in vivo for comprehensive antitumor therapy.

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“…27 Both HPLC and mass spectrometric analyses (see 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 14, 138-147. …”

Section: Maleimide Deprotection and Conjugation Reactions With Polyamunclassified

Protected Maleimide Building Blocks for the Decoration of Peptides, Peptoids, and Peptide Nucleic Acids

et al. 2013

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Monomers allowing for the introduction of [2,5-dimethylfuran]-protected maleimides into polyamides such as peptides, peptide nucleic acids and peptoids were prepared, as well as the corresponding oligomers. Suitable maleimide deprotection conditions were established in each case. The stability of the adducts generated by Michael-type maleimide-thiol reaction and Diels-Alder cycloaddition to maleimide deprotection conditions was exploited to prepare a variety of conjugates from peptide and PNA scaffolds incorporating one free and one protected maleimide. The target molecules were synthesized by using two subsequent maleimide-involving click reactions separated by a maleimide deprotection step. Carrying out maleimide deprotection and conjugation simultaneously gave better results than performing the two reactions subsequently.

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Conjugation Reactions Involving Maleimides and Phosphorothioate Oligonucleotides

Abstract: ABSTRACT

Cited by 19 publications

References 36 publications

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

Easy introduction of maleimides at different positions of oligonucleotide chains for conjugation purposes

Stressing the Role of DNA as a Drug Carrier: Synthesis of DNA–Drug Conjugates through Grafting Chemotherapeutics onto Phosphorothioate Oligonucleotides

Protected Maleimide Building Blocks for the Decoration of Peptides, Peptoids, and Peptide Nucleic Acids

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