Reversible covalent modification of DNA

Gohil, R. N.; Roth, Annette; Day, R.

doi:10.1016/0003-9861(74)90168-4

Cited by 4 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous investigations in our laboratories revealed that the facile alkylation of phosphodiesters with p -quinone methide 1 was promoted by a Brønsted acid (Scheme ) . In situ modification of DNA might be readily achieved through trialkyl phosphate formation, although this has proven quite challenging by reported approaches . Further development of a reagent for the selective alkylation of phosphodiesters has led us to study derivatives designed to stabilize the phosphotriester product in the quinone methide−phosphodiester alkylation equilibrium.…”

Section: Introductionmentioning

confidence: 99%

Trapping Phosphodiester−Quinone Methide Adducts through in Situ Lactonization

Zhou

Turnbull

2000

J. Org. Chem.

View full text Add to dashboard Cite

The goal of in situ modification of DNA via phosphodiester alkylation has led to our design of quinone methide derivatives capable of alkylating dialkyl phosphates. A series of catechol derivatives were investigated to trap the phosphodiester-quinone methide alkylation adduct through in situ lactonization. The catechol derivatives were uniquely capable of characterizable p-quinone methide formation for mechanistic clarity. These investigations revealed that with a highly reactive lactonization group (phenyl ester), lactonization competed with quinone methide formation. Lactone-forming groups of lower reactivity (methyl ester, n-propyl ester, and dimethyl amide) allowed quinone methide formation followed by phosphodiester alkylation; however, they were ineffective at in situ lactonization to drain the phosphodiester alkylation equilibrium to the desired phosphotriester product. The derivatives tethered with lactone-forming functionality of intermediate reactivity (chloro-, trichloro-, and trifluoroethyl esters), allowed quinone methide formation, phosphodiester alkylation, and in situ lactonization to efficiently afford the trapped phosphotriester adduct.

show abstract

Section: Introductionmentioning

confidence: 99%

Trapping Phosphodiester−Quinone Methide Adducts through in Situ Lactonization

Zhou

Turnbull

2000

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…However, to our knowledge there are no studies of quinone methide alkylation of the most abundant nucleophilic functional group of DNA: phosphodiesters. This is likely due to the relative weak nucleophilicity of phosphodiesters and known difficulty in directing alkylation to this functional group in nucleic acid polymers (Scheme ). − In developing a research program around the application of quinone methides to drug design, drug delivery, and biomolecular labeling, we have investigated the reactivity of a p -quinone methide with mildly nucleophilic phosphodiesters as models for nucleic acid polymers. We have found that phosphodiester alkylation with this p -quinone methide is possible when promoted by a Brønsted acid.…”

Section: Introductionmentioning

confidence: 99%

Phosphodiester Alkylation with a Quinone Methide

Zhou

Turnbull

1999

J. Org. Chem.

View full text Add to dashboard Cite

Despite the wide array of studies involving DNA alkylation and cleavage with quinone methide generating compounds, there have been no reports on the alkylation of phosphodiesters with quinone methides. We have investigated the reaction of dialkyl phosphates with a p-quinone methide in order to determine the potential for alkylation to produce trialkyphosphates. These studies have revealed that a phosphodiester can be alkylated with a p-quinone methide when promoted by a Brønsted acid. The role of the Brønsted acid is to sufficiently activate the p-quinone methide to allow phosphodiester addition to occur. The alkyl substituents of the phosphodiester have been found to effect the reactivity of the dialkyl phosphate under the reaction conditions examined. Equilibrium conversions up to 83% trialkyl phosphate formation have been achieved.

show abstract

Extrinsic cotton effect and helix‐coil transition in a DNA‐polycation complex

1977

View full text Add to dashboard Cite

SynopsisA strong, positive, extrinsic CD band ([8]242.5 = -2 X deg cm2/dmole) has been observed for a t~-bromo-poly[methylene-l,4-phenylenecarbonyloxyethylene(dimethylamino) bromide] (I). The extrinsic Cotton effect is attributed to the ordered arrangement of the aromatic chromophores along the DNA helix. The extrinsic band had a linear dependence on the amount of polycation I added from r 5 0.3 to r = 4 . 5 , but decreased thereafter. Addition of the polycation decreased the positive CD band of DNA a t 275 nm. The transformation of B -C form in the presence of salts or other polycations caused similar changes. The decrease in [8]275 was reversed a t higher concentrations of the polycation ( r > 0.4).Thermal denaturation studies indicated both stabilization of the helix conformation (Atrn = Zl°C) and a high degree of cooperativity in the melting of DNA-polycation complex as compared to native calf thymus DNA. Using the linear relationship between r (polycation residue/DNA phosphate) and F (fraction of bound base pairs), a value of 0.6 was derived for [j (number of monomer residues5f polycation/nucleotide).Both electrostatic and hydrophobic effects probably influence the stability of the DNApolycation complex, since the strength of the 242.5 nm CD band is a function of both salt and urea concentrations.

show abstract

Reversible covalent modification of DNA

Cited by 4 publications

References 24 publications

Trapping Phosphodiester−Quinone Methide Adducts through in Situ Lactonization

Trapping Phosphodiester−Quinone Methide Adducts through in Situ Lactonization

Phosphodiester Alkylation with a Quinone Methide

Extrinsic cotton effect and helix‐coil transition in a DNA‐polycation complex

Contact Info

Product

Resources

About