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Biomedical subjects

G Rodighiero

Publications and source records attributed to G Rodighiero.

At least 37 records · Page 2Linked to original sources

Studies on the mechanism of action of mitomycin C.

The in vitro formation and properties of the molecular complex between mitomycin C and native DNA were examined by means of various experimental methods; the data obtained indicate that the complex is extremely weak and that the chromophoric moiety of the antibiotic is not involved in its formation. The alkylating activity of mitomycin C was also studied using 3H-mitomycin C; while monofunctional alkylation increases almost in parallel with the concentration of the antibiotic, the difunctional alkylation, causing inter-strand cross-linkages in DNA, rapidly reaches a maximum and then remains constant even when increasing the concentration of the antibiotic and monofunctional alkylation. On the basis of these results, the currently accepted molecular model of the mitomycin--DNA interaction must be revised; a new model of this interaction is presented, which is in better agreement with the properties of mitomycin C and with the latest findings on the subject.

Alkylation↗

The binding of 8-methoxypsoralen by human serum albumin.

The ability of 8-methoxypsoralen (8-MOP) to bind human serum albumin has been investigated in vitro through equilibrium dialysis and fluorescence quenching. By means of the first technique it was observed that, at concentrations presumably close to those obtainable in vivo following its administration in the photochemotherapy of psoriasis, over 80% of 8-MOP was bound to serum albumin. In human serum albumin fluorescence techniques revealed a preferential site of binding for 8-MOP with a high binding constant (Ka = 0.7 X 10(5) M-1) and precise steric requirements, since small conformational variations of the protein molecule were able to abolish its affinity for furocoumarin.

Dialysis↗

DNA receptor sites for the intercalation of nogalamycin.

The intercalation of the planar chromophoric moiety of nogalamycin between two base pairs of duplex DNA has been evidenced by means of low-dichroism measurements. The possible presence of specific binding sites for mogalamycin on DNA has been suggested by studies on the denaturation and renaturation of DNA complexed with nogalamycin. A clear evidence was obtained by investigating the interaction of nogalamycin with polydeoxyribonucleotides containing known, regularly repeating sequences, used as model compounds. The results obtained with these polymers and the DNA suggest that the segment containing both purine (A,G) anf pyrimidine (T,C) bases in alternate sequences is the preferential receptor site on the DNA. A decreasing affinity is exhibited by poly d(A--T)-poly d(A--T), poly d(G--C)-poly d(G--C) and poly dG-poly dC segments, in the order. The poly dA-poly dT sequence appears to be closed to the interaction of nogalamycin.

Animals↗

Receptor sites of DNA for the photoreaction with psoralen.

Biological and pharmacological effects of psoralens are correlated to their capacity to photoreact with pyrimidine bases of native DNA and in particular to form inter-strand cross-linkages. To determine possible prefenrential sites for the photoreaction the Authors have studied the capacity of psoralen to form complexes and to photoreact with various polynucleotides. The Authors have shown that specific sites exist in DNA for the photochemical interaction with psoralen; these sequences which can be considered as specific receptors for photobiological activity of psoralen are represented by alternate sequences in every strand of A and T, corresponding to poly d(A--T) - poly d(A--T). These receptor sites show a high capacity for intercalation and successive photoreaction with psoralen.

Animals↗