Interactions of Molecules with Nucleic Acids. X. Covalent Intercalat e Binding of the Carcinogenic BPDE I(+) to Kinked DNA

Abstract

A theoretical model is proposed for the covalent binding of (+) 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene denoted by BPDE I(+), to N2 on guanine. The DNA must kink a minimum of 39 degrees to allow proper hybrid configurations about the C10 and N2 atoms involved in bond formation and to allow stacking of the pyrene moiety with the non-bonded adjacent base pair. Conservative (same sugar puckers and glycosidic angles as in B-DNA) and non-conservative (alternating sugar puckers as in intercalation sites) conformations are found and they are proposed structures in pathways connecting B-DNA, an intercalation site, and a kink site in the formation of a covalently intercalative bound adduct of BPDE I(+) to N2 on guanine. Stereographic projections are presented for (3') and (5') binding in the DNA. Experimental data for bending of DNA by BPDE, orientation of BPDE in DNA and unwinding of superhelical DNA is explained. The structure of a covalent intercalative complex is predicted to result from the reaction. Also, an anti----syn transition of guanine results in a structure which allows the DNA to resume its overall B-form. The only change is that guanine has been rotated by 200 degrees about its glycosidic bond so that the BPDE I(+) is bound in the major groove. The latter step may allow the DNA to be stored with an adduct which may produce an error in the genetic code.

Domestic Thermodynamics or How Not to Burn the Brownies, Explained

“…Some of these known PAHs are known carcinogens. Such PAHs react with DNA in specific and potentially harmful ways (Taylor, Miller & Bleyer, 1983;Miller, Taylor, Dommen & Burbaum, 1985). Read this carefully: Dependent upon the extent to which the burning has gone, a potential for production of such PAHs in a burned baking product may arise.…”

Aflatoxin B1 and DNA Adducts. Proposed Model for Surface Noncovalent and Covalent Complexes with N(7) of Guanine. II.

“…The departure of adjacent base pairs from parallel planarity results in a wedged-shaped opening referred to as kinking (ax). The kink angle ax is positive for kinks opening into the minor groove of DNA and negative for kinks opening into the major groove of DNA ( 49). a tendency to maximize interactions by modest alterations in the bond angle about N(7).…”

Sequence Selectivity, a Test of the Nature of the Covalent Adduct Formed Between Benzo[a]pyrene and DNA

“…[17][18][19][20][21][22][23]. These studies while providing useful information on the different possible mechanisms and structures did not permit to make a clear cut choice between them and did not thus permit in particular to solve the dilemma about the pre-eminence of exteriorly bound or intercalative covalent association.…”