| Research Abstract |
Pradimicin A and its derivative BMY-28864 with anti-HIV and anti-fungal activities have been shown to be carbohydrate-binding antibiotics belonging to a novel category by our recent studies. In this study, for 17 Pradimicin A derivatives whose structures had been clarified but whose carbohydrate-binding activity and anti-HIV activity were unknown, the ability, specificity, and affinity of their binding to oil-gosaccharide chains were investigated using HIV glycoprotein gpl2O, various natural and artificial glycoproteins, and artificial glycohipids not only to develop a more effective anti-HIV carbohydrate-binding agent using the derivatives as lead compounds, but also to obtain drug design information for new agents against other bacterial and viral infections. The results showed that four of the 17 Pradimicin A derivatives examined exhibited a carbohydrate-binding activity as in the case of Pradimicin A and BMY-28864, and that three of them showed a stronger binding affinity than Pradimicin A and BMY-28864. These findings suggest that these substances are of carbohydrate-binding and very promising also as an anti-HIV agent. Interestingly, one of the four derivatives with carbohydrate-binding nature did not have any anti- fungal effect. Therefore, more accurate information about intramolecular sites required for the drug design could be obtained through detailed investigations on the relationship between the structure, carbohydrate-binding activity, and physiologicaleffects of these substances and on recognition sites in oligosaccharide chains. In addition, a stable conformation of Pradimicin A under vacuum condition could be figured by calculation. The findingss in this study are therefore considered to serve as an important drug design information for the development of more potent and effective anti-HIV agents with carbohydrate-binding property in the future.
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