Lectins are proteins that recognize specific carbohydrate structures and thereby participate in molecular recognition events of fundamental relevance in a variety of biological processes [1]. They are promising ligands for targeted drug delivery because they bind rapidly and specifically to membrane-linked carbohydrates or glycoproteins to initiate receptor-mediated endocytosis [2]. In recent years several lectin-functionalized nanoparticles have been described and, in particular, the well-known wheat germ agglutinin has been used for the selective delivery of nanoparticles loaded with a widely used anticancer agent [3]. In our laboratory we have begun to characterize a novel lectin that presents a significant sequence homology with wheat germ agglutinin and exhibits cytotoxic activity against epithelial cancer cells (Fig. 1). The lectin is isolated in very high yields (500 mgs per Kg of the starting material) and with a very simple purification method from the rhizomes of the common giant reed Arundo donax, one of the most readily available sources of biomass on the Earth because of its fast growing rate and its ability to grow in different soil types and climatic conditions. We call the protein ADL which stands for Arundo donax lectin [4]. The goal of our project is to structurally and functionally characterize the lectin, i.e. to define in detail its ligand binding specificity using several biophysical techniques and, in particular, X-ray crystallography. We have already prepared diffraction quality crystals and are in the process of solving its three-dimensional structure. In the future we intend to prepare ADL conjugated nano-sized particles for the selective delivery of anti-tumoral agents to neoplastic epithelial cells. [1] Debbage P. Targeted drugs and nanomedicine: present and future. Curr Pharm Des., 2009;15(2):153-72. [2] C.M. Lehr, Lectin-mediated drug delivery: the second generation of bioadhesives, J. Control. Release, 2000; 65:19–29. [3] Mo Y, Lim LY. Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate. J. Control. Release, 2005; 107(1):30-42. [4] Kaur A, Singh J, Kamboj SS, Sexana AK, Pandita RM, Shamnugavel M. Isolation of an N-acetyl-D-glucosamine specific lectin from the rhizomes of Arundo donax with antiproliferative activity Phytochemistry, 2005; 66(16):1933-1940.

Unraveling the antitumoral properties of Arundo donax lectin

PERDUCA, Massimiliano;BOVI, Michele;Destefanis, Laura;BONACONSA, Marta;MONACO, Ugo Luigi
2015-01-01

Abstract

Lectins are proteins that recognize specific carbohydrate structures and thereby participate in molecular recognition events of fundamental relevance in a variety of biological processes [1]. They are promising ligands for targeted drug delivery because they bind rapidly and specifically to membrane-linked carbohydrates or glycoproteins to initiate receptor-mediated endocytosis [2]. In recent years several lectin-functionalized nanoparticles have been described and, in particular, the well-known wheat germ agglutinin has been used for the selective delivery of nanoparticles loaded with a widely used anticancer agent [3]. In our laboratory we have begun to characterize a novel lectin that presents a significant sequence homology with wheat germ agglutinin and exhibits cytotoxic activity against epithelial cancer cells (Fig. 1). The lectin is isolated in very high yields (500 mgs per Kg of the starting material) and with a very simple purification method from the rhizomes of the common giant reed Arundo donax, one of the most readily available sources of biomass on the Earth because of its fast growing rate and its ability to grow in different soil types and climatic conditions. We call the protein ADL which stands for Arundo donax lectin [4]. The goal of our project is to structurally and functionally characterize the lectin, i.e. to define in detail its ligand binding specificity using several biophysical techniques and, in particular, X-ray crystallography. We have already prepared diffraction quality crystals and are in the process of solving its three-dimensional structure. In the future we intend to prepare ADL conjugated nano-sized particles for the selective delivery of anti-tumoral agents to neoplastic epithelial cells. [1] Debbage P. Targeted drugs and nanomedicine: present and future. Curr Pharm Des., 2009;15(2):153-72. [2] C.M. Lehr, Lectin-mediated drug delivery: the second generation of bioadhesives, J. Control. Release, 2000; 65:19–29. [3] Mo Y, Lim LY. Preparation and in vitro anticancer activity of wheat germ agglutinin (WGA)-conjugated PLGA nanoparticles loaded with paclitaxel and isopropyl myristate. J. Control. Release, 2005; 107(1):30-42. [4] Kaur A, Singh J, Kamboj SS, Sexana AK, Pandita RM, Shamnugavel M. Isolation of an N-acetyl-D-glucosamine specific lectin from the rhizomes of Arundo donax with antiproliferative activity Phytochemistry, 2005; 66(16):1933-1940.
Arundo donax lectin, Antitumoral properties, X-ray crystallography
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/927071
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