Difluoro-C4′-oxidized Abasic Site for Efficient Amine Modification in Biological Systems

Yang, Bo; Jinnouchi, Akiko; Shimizu, Hiroshi; Aso, Mariko

doi:10.1021/ol302703m

Cited by 2 publications

(7 citation statements)

References 19 publications

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“…Reactions of 7, 8, and 9 with a Proximal Amine on Complementary Strand 15. The reactivities of the dicarbonyl-carrying ODNs 8 and 9 with an amine were evaluated in the context of duplexes containing 15, 9,26 in which the aliphatic amino group of 15 could approach dicarbonyls (Scheme 3).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Recently, we reported the reaction of an ODN containing a 2,2-difluoro analog of C4′-OAS. 9 In this case, cross-link formation proceeded efficiently without the addition of reagents.…”

Section: Bioconjugation Of Oligodeoxynucleotides (Odns) With Biomolecmentioning

confidence: 95%

“…Recently, we reported the reaction of an ODN containing a 2,2-difluoro analogue of C4′-OAS. 9 In this case, cross-link formation proceeded efficiently without the addition of reagents. However, the reaction rate was unfavorably slow compared to reductive amination of OAS duplexes.…”

Section: Bioconjugate Chemistrymentioning

confidence: 95%

“…3,4 Nucleic acids containing carbonyl groups have been used extensively for conjugate formation and labeling applications. [5][6][7][8][9] The reactivity of the carbonyl groups and their stability in aqueous environments are advantageous for the modification of biomolecules at naturally available amino groups. An ODN containing an abasic site is an example of such a reactive species; the predominant ring-closed form exists in equilibrium with the ringopened form (1) bearing an aldehyde group at the C1-position of deoxyribose (C1-aldehyde).…”

Section: Bioconjugation Of Oligodeoxynucleotides (Odns) With Biomolecmentioning

confidence: 99%

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Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues

et al. 2015

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We evaluated the efficacy of bioconjugation of oligodeoxynucleotides (ODNs) containing 1,4-dicarbonyl groups, a C4'-oxidized abasic site (OAS), and a newly designed 2'-methoxy analogue, via reductive amination with lysine residues. Dicarbonyls, aldehyde and ketone at C1- and C4-positions of deoxyribose in the ring-opened form of OAS allowed efficient reaction with amines. Kinetic studies indicated that reductive amination of OAS-containing ODNs with a proximal amine on the complementary strand proceeded 10 times faster than the corresponding reaction of an ODN containing an abasic site with C1-aldehyde. Efficient reductive amination between the DNA-binding domain of Escherichia coli DnaA protein and ODNs carrying OAS in the DnaA-binding sequence proceeded at the lysine residue in proximity to the phosphate group at the 5'-position of the OAS, in contrast to unsuccessful conjugation with abasic site ODNs, even though they have similar aldehydes. Theoretical calculation indicated that the C1-aldehyde of OAS was more accessible to the target lysine than that of the abasic site. These results demonstrate the potential utility of cross-linking strategies that use dicarbonyl-containing ODNs for the study of protein-nucleic acid interactions. Conjugation with a lysine-containing peptide that lacked specific affinity for ODN was also successful, further highlighting the advantages of 1,4-dicarbonyls.

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Section: ■ Results and Discussionmentioning

confidence: 99%

“…Recently, we reported the reaction of an ODN containing a 2,2-difluoro analog of C4′-OAS. 9 In this case, cross-link formation proceeded efficiently without the addition of reagents.…”

Section: Bioconjugation Of Oligodeoxynucleotides (Odns) With Biomolecmentioning

confidence: 95%

Section: Bioconjugate Chemistrymentioning

confidence: 95%

Section: Bioconjugation Of Oligodeoxynucleotides (Odns) With Biomolecmentioning

confidence: 99%

See 2 more Smart Citations

Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues

et al. 2015

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“…Many gemcitabine synthesis strategies have been employed, especially those building enantioenriched nucleosides starting from natural sugars. This strategy bypasses the need for anomeric activation at the oxygen atom by synthesis of enantioselective prefabricated building blocks in which an appropriate leaving group, necessary during the coupling reaction with the nucleobase, is selectively introduced in the de novo synthetic sequence [ 36 , 37 , 38 , 39 ]. Other approaches also focused on modifying either the substituted nucleoside or the nucleobase [ 40 , 41 , 42 ].…”

Section: Gemcitabinementioning

confidence: 99%

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

et al. 2017

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Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

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Difluoro-C4′-oxidized Abasic Site for Efficient Amine Modification in Biological Systems

Cited by 2 publications

References 19 publications

Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues

Bioconjugation of Oligodeoxynucleotides Carrying 1,4-Dicarbonyl Groups via Reductive Amination with Lysine Residues

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery

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