Thermodynamic studies on the interaction of water-soluble porphyrins with the glucose/mannose-specific lectin from garden pea (Pisum sativum)

Abstract

SummaryDue to the application of porphyrins as photosensitizers in photodynamic therapy to treat cancer, and the ability of some lectins to preferentially recognize tumor cells, studies on the interaction of porphyrins with lectins are of considerable interest. Here we report thermodynamic studies on the interaction of several free-base and metallo-porphyrins with pea (Pisum sativum) lectin (PSL). Association constants (K a ) were obtained by absorption titrations by monitoring changes in the Soret band of the porphyrins and the K a values obtained for various porphyrins at different temperatures are in the range of 1.0 6 10 4 to 8.0 6 10 4 M 71 . Both cationic and anionic porphyrins were found to bind to PSL with comparable affinity. Presence of 0.1 M methyl-a-D-mannopyranoside -a carbohydrate ligand that is specifically recognised by PSLdid not affect the binding significantly, suggesting that porphyrin and sugar bind at different sites on the lectin. From the temperature dependence of the K a values, the thermodynamic parameters, change in enthalpy and change in entropy associated with the binding process were estimated. These values were found to be in the range: DH8 ¼ 795.4 to 733.9 kJ Á mol 71 and DS8 ¼ 7237.2 to 732.2 J Á mol 71 Á K 71 , indicating that porphyrin binding to pea lectin is driven largely by enthalpic forces with the entropic contribution being negative. Enthalpy-entropy compensation was observed in the interaction of different porphyrins to PSL, with the exception of meso-tetra-(4-sulfonatophenyl)porphyrinato zinc(II), emphasizing the role of water structure in the overall binding process. Circular dichroism and differential scanning calorimetric studies indicate that while porphyrin binding does not induce significant changes in the lectin structure and thermal stability, carbohydrate binding induces moderate changes in the tertiary structure of the protein and also increases its thermal unfolding temperature and the enthalpy of the unfolding transition.IUBMB Life, 58: 720-730, 2006

Interaction of Wheat Germ Agglutinin with Porphyrin Compounds—Potential Anticancer Agents

“…An alternative approach has been studied and applied using some plant lectins, such as snake gourd Trichosanthes anguina, legume Concanavalin A, and pea lectin, that have been found to bind porphyrins and may have potential application in targeted PDT (3,12,13,14,17,20,22). Our data are the first to demonstrate the porphyrin binding capacity of WGA lectin.…”

“…Therefore, in order to improve the selective recognition of tumour cells by porphyrins, several plant lectins have been tested as drug delivery agents for these sensitizers (11). Previous spectroscopic and crystallographic studies have shown that some plant lectins (snake gourd Trichosantes anguina seed lectin, concanavalin A, peanut lectin, jacalin) can bind porphyrins (3,12,13,14,17,22,20).…”

Plant Lectins Targeting O-Glycans at the Cell Surface as Tools for Cancer Diagnosis, Prognosis and Therapy

“…The non-covalent binding between porphyrins and different T/Tn-specific lectins including jacalin from the Jackfruit ( Artocarpus integrifolia ) [195], the snake gourd ( Trichosanthes aguina ) [196], and the bitter gourd ( Momordica charantia ) [197], was investigated. The binding of lectins to porphyrin and phycobilin molecules was further extended to the T/Tn-specific lectin PNA [198] and to other legume lectins such as the mannose-specific concanavalin A [199] and the garden pea lectin [200]. The interaction of jacalin with phycobilin, another photosensitizing molecule, was also studied [201].…”

Chemical Synthesis and Medicinal Applications of Glycoporphyrins

“…Here, cationic and anionic porphyrins displayed similar affinity while 639b showed the strongest affinity for PSL compared to other porphyrin derivatives, possibly due to axial interactions of the Zn(II) metal ion with the protein. Introduction of the methyl-α-D-mannopyranoside, a specific substrate for PSL, showed no effect on the porphyrin binding determining the presence of different binding sites on the lectin [393] . The temperature dependence of the K a values were used to evaluate the thermodynamic forces that influence the interaction.…”