Interaction of porphyrins with concanavalin a and pea lectin

Currently porphyrins are used as photosensitizers in photodynamic therapy for the treatment of cancer. However, this approach suffers due to the inability of many porphyrin-based drugs to accumulate preferentially in tumours. In view of this, we considered if the carbohydrate-binding proteins, lectins, which preferentially recognize malignant cells, could be used for the targeting of porphyrins to tumour cells. In the present study, we have investigated the interaction of a free base porphyrin, meso-tetrasulphonatophenylporphyrin and the corresponding metal derivative, meso-zinc-tetrasulphonatophenylporphyrin with two legume lectins, concanavalin A and pea (Pisum sativum) lectin. Each lectin subunit was found to bind one porphyrin molecule and the association constant, Ka, estimated from absorption and fluorescence titrations at room temperature (28 +/- 1 degree centigrade) was in the range of 1.2 X 10 to the power of 4 M to the power of -1 to 6.3 X 10 to the power of 4 M to the power of -1. Both free lectin and lectin saturated with the specific saccharide were found to bind the porphyrin with comparable binding strength, indicating that porphyrin binding takes place at a site different from the sugar-binding site. These results indicate that lectins may potentially serve as drug-delivery agents for porphyrin sensitizers in photodynamic therapy

Binding of porphyrins by the tumor-specific lectin, Jacalin [jack fruit (Artocarpus integrifolia) agglutinin]

Jacalin (Artocarpus integrifolia agglutinin) specifically recognizes the tumor-associated T-antigenic disaccharide structure, Galβ13GalNAc. Porphyrins and their derivatives are currently used as photosensitizers in photodynamic therapy to treat malignant tumors. In this study, the interaction of several free base porphyrins and their metalderivatives with jacalin is investigated by absorption and fluorescence spectroscopy. Each lectin subunit was found to bind one porphyrin moleculeand the association constants were estimated to be in the range of 2.4×103M–1 to 1.3×105M–1 at room temperature for the interaction of different porphyrins with jacalin. These values are in the same range as those obtained for the interaction of monosaccharidesto jacalin. Both free lectin and lectin saturated with the specific saccharide were found to bind different porphyrins with comparable binding strength indicating that porphyrin binding takes place at a site differentfrom the sugar binding site. Further, both anionic and cationic porphyrins were found to interact with the lectin with comparable affinity, clearly indicating that the charge on the porphyrin does not play any role in the binding process and that most likely the interaction is mediated by hydrophobic forces. These results suggest that jacalin and other lectins may potentially be useful for targeted delivery of porphyrins to tumor tissues in photodynamic therapy