The interaction of actinomycin with DNA: requirement for the 2-amino group of purines.

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Abstract
In contrast to the A-T [adenine-thymine] base pair, with its 2 H-bonds, the DAP-T [2,6-diaminopurine-thymine], like the G-C [guanine-cytosine] pair, might be expected to form 3 H-bonds. The higher Tm [transition temperature] of dDAP-T [deoxynucleotide copolymer with an alternating sequence of diaminopurine and thymine residues], as compared with dAT [alternating deoxynucleotide copolymer of adenine and thymine], is consistent with this assumption. The formation of the additional H-bond in this case, as in the G-C base pair, is correlated also with a substantial increase in buoyant density of the polymer. Due to the location of its 2 amino groups, DAP [diamino purine] is structurally similar in some respects to both adenine and guanine. However, its chemical and biochemical properties make DAP an analogue of adenine, not of guanine. Thus, in its pK values, base pairing pattern, and substrate behavior for enzymes DAP closely resembles only adenine, not guanine. The 2-amino group of DAP differs significantly from that of guanine in its susceptibility to chemical deamination. These facts make it reasonable to conclude that the DAP-T base pair is analogous to the A-T base pair chemically, as well as in the distribution of its functional groups; the outstanding property which DAP-T and G-C pairs have in common is a purine 2-amino group and its location in the minor groove of helical DNA. When AM [actinomycin] forms complexes with native DNA, the spectrum of the antibiotic changes, and the buoyant density, thermal stability, and template function of the DNA are markedly affected. The interaction of AM with dDAP-T faithfully reproduces (and in some respects exaggerates) each of these qualities of AM-DNA complexes. dAT does not interact with AM, and dDAP-T differs from dAT in its possession of the additional purine 2-amino groups. Thus, the introduction of a purine 2-amino group into the minor groove of helical DNA is sufficient, and perhaps the sole requirement, for converting a base pair from AM resistance (and Mithramycin resistance) to AM sensitivity (and Mithramycin sensitivity).