Abstract Title:

Stereochemical modelling studies of the interaction of antineoplaston A10 with DNA.

Abstract Source:

Drugs Exp Clin Res. 1987 ;13 Suppl 1:77-81. PMID: 3569020

Abstract Author(s):

L B Hendry, T G Muldoon, S R Burzynski, J A Copland, A F Lehner

Abstract:

Antineoplaston A10 (3-phenylacetylamino-2,6-piperidinedione), a peptide analogue originally isolated from human urine, has been demonstrated to fit between base pairs in DNA. Examination of the fit of A10 into the 10 possible sites in unwound DNA using published criteria revealed a preference, but not absolute specificity, for the sequence 5'-dTdT-3' X 5'-dAdA-3'. Good fits were also observed for the sequences 5'-dTdC-3' X 5'-dGdA-3' and 5'-dCdT-3' X 5'-dAdG-3'. In each case at least one stereospecific hydrogen bond was possible between the imino proton of the piperidinedione ring stacked between the two pyrimidines and a neighbouring phosphate oxygen of the DNA backbone. These findings support the prediction that A10 may interact reversibly with DNA and thereby compete with carcinogens that form covalent linkages with DNA (e.g., arene oxides). It follows that such interactions should prevent the growth of tumours induced by various carcinogens.

Study Type : In Vitro Study
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