Lectins, Interconnecting Proteins with Biotechnological/Pharmacological and Therapeutic Applications

Abstract

Lectins are proteins extensively used in biomedical applications with property to recognize carbohydrates through carbohydrate-binding sites, which identify glycans attached to cell surfaces, glycoconjugates, or free sugars, detecting abnormal cells and biomarkers related to diseases. These lectin abilities promoted interesting results in experimental treatments of immunological diseases, wounds, and cancer. Lectins obtained from virus, microorganisms, algae, animals, and plants were reported as modulators and tool markers in vivo and in vitro; these molecules also play a role in the induction of mitosis and immune responses, contributing for resolution of infections and inflammations. Lectins revealed healing effect through induction of reepithelialization and cicatrization of wounds. Some lectins have been efficient agents against virus, fungi, bacteria, and helminths at low concentrations. Lectin-mediated bioadhesion has been an interesting characteristic for development of drug delivery systems. Lectin histochemistry and lectin-based biosensors are useful to detect transformed tissues and biomarkers related to disease occurrence; antitumor lectins reported are promising for cancer therapy. Here, we address lectins from distinct sources with some biological effect and biotechnological potential in the diagnosis and therapeutic of diseases, highlighting many advances in this growing field.

Figure 1

Lectins induced in vitro mitogenic activation of T cells (a) and stimulated in vivo Th1, Th2, and Th17 responses (b).

Figure 2

Histologic micrographs of wounds treated with Cramoll 1,4 and Con A in the 12th day in female albino Swiss mice. A total wound closure, reepithelialization, and deposition of collagen fibers are observed in Cramoll 1,4 treated group with 5 µg/100 µl (a), Cramoll 1,4 treated group with 10 µg/100 µl (b), and Con A (10 µg/100 µl) treated group (c). The formation of well-developed cutaneous annexes is present in Cramoll 1,4 (10 µg/100 µl) treated group (b). Incomplete reepithelialization without wound closure observed for control negative group administered with 150 mM NaCl (d).

Figure 3

Differential interaction of lectins with cells expressing diverse glycosylation pattern. Mucins constitute a glycosylated protein family with high molecular weight, expressed by epithelial tissues. In normal cells (a) the mucin is extensively glycosylated and more than 50% of its molecular mass corresponds to oligosaccharide chains, which may be difficult or impair the interaction of lectins and the carbohydrate residues from mucin. On the other hand, in its tumor counterparts (b), the mucin generally has fewer oligosaccharide side chains, which may facilitate the binding between lectins and glycosylated sites. ECM = extracellular medium; ICM = intracellular medium.

Figure 4

Mechanism of lectin bioadhesion. Glycoconjugates on cell surface (glycoproteins or glycolipids) can operate as lectin binding sites. ECM = extracellular medium; ICM = intracellular medium.

Figure 5

Schematic representation of lectin histochemistry using peroxidase-conjugated lectins. In this hypothetical case, the lectin binds glycan moieties more expressed on normal tissues, which suffer a modification in their structure (e.g., sialylation or fucosylation) in benign and malign tumors tissues. Thus, the lectin binding increased in transformed tissues. The DAB reagent in the presence of peroxidase and hydrogen peroxide was converted to DAB oxidized that precipitates as a brown product and allows visualization of lectin binding.

Figure 6

Schematic representation of lectin-modified electrode surface before (a) and after binding (b) for measurements of lectin-glycan interactions. In the electrochemical system, measurements are performed in a solution containing a redox probe (e.g., [Fe(CN)₆]^3−/4−); reduction or oxidation states generate electrochemical signals (charge transfer resistance for electrochemical impedance spectroscopy, EIS, and current for differential pulse voltammetry, DPV) to monitor electrode surface interactions. Before binding (a), charge transfer resistance or current signals are obtained on lectin-modified electrode surface. After binding (b), the presence of cells or glycoproteins on electrode surface generates a higher blockage for charge transfer and current signals. It is measured as an increase in the charge transfer resistance (represented by semicircle A′) for EIS response and a reduction in the current amplitude for DPV response.