Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages

Agarwal, Kan; Riftina, Faina

doi:10.1093/nar/6.9.3009

Cited by 75 publications

(31 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…NH40H should not cause undue degradation. 18 However, our finding of 30% product degradation in two hours makes use of conc. NH40H prohibitive even for those short periods, if product yield is of any importance.…”

Section: Discussionmentioning

confidence: 82%

Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure

Hogrefe¹,

Vaghefi²,

Reynolds³

et al. 1993

Nucl Acids Res

View full text Add to dashboard Cite

Deprotection of methylphosphonate oligonucleotides with ethylenediamine was evaluated in a model system. Methylphosphonate sequences of the form 5'-TTTNNTTT, where N was either N4-bz-dC, N4-ibu-dC, N2-ibu-06-DPC-dG, N2-ibu-dG, N6-bz-dA, or T, were used to determine the extent of modifications that occur during deprotection. Up to 15% of N4-bz-dC was found to transaminate at the C4 position when treated with ethylenediamine. A similar displacement reaction with ethylenediamine was observed at the 06 position of N2-ibu-06-DPC-dG, and to a much lesser extent of N2-ibu-dG. Side reactions were not observed when oligonucleotides containing N4-ibu-dC, N6-bz-dA, or T were treated with ethylenediamine. A novel method of deprotecting methylphosphonate oligonucleotides was developed from these studies. The method incorporates a brief treatment with dilute ammonia for 30 minutes followed by addition of ethylenediamine for 6 hours at room temperature to complete deprotection in a one-pot format. The solution is then diluted and neutralized to stop the reaction and prepare the crude product for chromatographic purification. This method was used to successfully deprotect a series of oligonucleotides at the 1, 100, and 150 j.mole scales.These deprotection results were compared to a commonly used two-step method and found to be superior in yield of product by as much as 250%.

show abstract

Section: Discussionmentioning

confidence: 82%

Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure

Hogrefe¹,

Vaghefi²,

Reynolds³

et al. 1993

Nucl Acids Res

View full text Add to dashboard Cite

show abstract

“…[13,15,36] In entry 1 (Table 5), a protected tyrosine triflate derivative 4 in the reaction with diethyl H-phosphonate was successfully converted into the corresponding arylphosphonate 9 in high yield. Entry 2 (Table 5) shows the transformation of cholesteryl H-phosphonate diester 5 into the highly lipophilic 2-naphthylphosphonate derivative 10.…”

Section: Synthesis Of Arylphosphonate Diesters Promoted By the Acetatmentioning

confidence: 99%

Preparation of Arylphosphonates by Palladium(0)‐Catalyzed Cross‐Coupling in the Presence of Acetate Additives: Synthetic and Mechanistic Studies

Kalek¹,

Jezowska²,

Stawiński³

2009

Adv Synth Catal

147

View full text Add to dashboard Cite

An efficient protocol for the synthesis of arylphosphonate diesters via a palladium-catalyzed cross-coupling of H-phosphonate diesters with aryl electrophiles, promoted by acetate ions, was developed. A significant shortening of the cross-coupling time in the presence of the added acetate ions was achieved for bidentate and monodentate supporting ligands, and for different aryl electrophiles (iodo, bromo and triflate derivatives). The reaction conditions were optimized in terms of amount of the catalyst, supporting ligands, and source of the acetate ion used. Various arylphosphonates, including those of potential biological significance, were synthesized using this newly developed protocol. Some mechanistic aspects of the investigated reactions are also discussed.

show abstract

“…N-Methylimidazole, mesitylene sulfonyl chloride, and dimethoxytrityl (Dmt) chloride were purchased from Aldrich. Methylphosphonate dichloride was synthesized according to a published procedure (7).…”

mentioning

confidence: 99%

B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates.

Callahan¹,

Han²,

Watt³

et al. 1986

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The simulation of the B-Z-DNA transition by using space-filling models of the dimer d(C-G) shows the possibility of hydrogen-bond formation between the N-2 amino group of the partially rotated guanine and one of the 5'-phosphate oxygens of deoxyguanylic acid. To probe the importance of this postulated interaction, analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, which replaced the first 5'-phosphate linkage of deoxyguanosine. The CD spectra in high salt concentration showed that the hexamer containing a methylphosphonate linkage with the Rp stereochemistry formed Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage with the Sp stereochemistry did not form Z-DNA. These results are consistent with a mechanism in which an interaction between the N-2 amino group of guanine and the prochiral Sp oxygen of deoxyguanosine 5'-phosphate kinetically controls the formation of Z-DNA. A water bridge between the N-2 amino group ofguanine and the 3'-phosphate oxygen of deoxyguanylic acid has been implicated in the stabilization of Z-DNA. To probe the importance of this water bridge, two additional analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, that replaced the first deoxyguanosine 3'-phosphate. The CD spectra showed that the hexamer containing a methylphosphonate linkage of the Rp stereochemistry underwent the transition to Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage of the Sp stereochemistry underwent the transition to Z-DNA to a 35% lesser extent. Thus the water bridge involving the prochiral Sp oxygen provides modest stabilization energy for Z-DNA. These studies, therefore, suggest that the B-Z-DNA transition is regulated both thermodynamically and kinetically through hydrogen-bond interactions involving phosphate oxygens and the N-2 amino group of guanine.Pohl and Jovin (1) showed that the alternating copolymer poly[d(C-G)] underwent a salt-induced conformational change. The new species thus formed was left-handed Z-

show abstract

Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages

Cited by 75 publications

References 11 publications

Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure

Deprotection of methylphosphonate oligonucleotides using a novel one-pot procedure

Preparation of Arylphosphonates by Palladium(0)‐Catalyzed Cross‐Coupling in the Presence of Acetate Additives: Synthetic and Mechanistic Studies

B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates.

Contact Info

Product

Resources

About