Protein-carbohydrate interactions inhibition

Goldstein L, Hollerman C, Smith EE. Protein-carbohydrate interaction. II. Inhibition studies on interaction of concanavalin A with polysaccharides. Biochemistry 1965, 4, 876-883. 

Overview and Future Development Inhibition of Protein-Carbohydrate Interactions... 

The mechanism of lectin-like cell-cell interactions has been established to explain yeast flocculation (Speers et al., 1998). Lectins are a structurally diverse group of proteins that are capable of binding carbohydrates while zymolectin is an anchored yeast cell wall protein that contains one or more mannose binding sites (Boulton Quain, 2001). This mechanism proposes that specific surface proteins known as zymolectins, which are present on flocculent yeast cells, bind to mannose residues of mannan molecules on neighbouring cell surfaces (Speers et al., 1998). The involvement of this protein-carbohydrate interaction was suggested by Taylor and Orton (Taylor Orton, 1978), as flocculation can be inhibited specifically by mannose. 

Discussion of the effect of ligand structure on protein-carbohydrate affinity requires an evaluation of complex stability constants. A munber of biophysical techniques are appropriate for the study of protein-carbohydrate interaction many of the more enlightening strategies are the topics of separate chapters elsewhere in this volume. We describe below three techniques used extensively in glycobiology— inhibition of hemagglutination, enzyme-linked lectin assay (ELLA), and isothermal titration microcalorimetry—and we consider the types of information provided by each technique in order to facilitate appropriate interpretation of the data. 

Protein-tannin interactions appear to be inhibited by the presence of some carbohydrates in solution [32, 65, 78, 81, 82]. This is particularly evident in the graph of Figure 16.5. 

Research work performed in the end of the last century by Haslam and co-workers showed that carbohydrates inhibit the protein-tannin interactions in solution (Luck et al. 1994 Ozawa et al. 1987). More recently, similar findings have been reported by de Freitas and co-workers using nephelometric techniques (Fig. 9D.12) for different carbohydrates and protein-tannin systems (Carvalho et al. 2006a, b de Freitas et al. 2003 Mateus et al 2004a). 

Fig. 9D.13 Mechanism of carbohydrate inhibition of protein tannin interactions (Mateus et al. 2004) (adapted from Mateus et al. 2004a)...

The SLe epitope is expressed on inflammation-induced acute phase proteins which serve as endogenous competitors for selectins and mediate a dampening of the immune response, returning inflammation to homeostasis [53]. Inhibitors of the selectins have been proposed to be useful therapies for treating inflammatory disorders including respiratory distress [54], hypersensitivity responses [55], and surgically induced myocardial ischemic reperfusion injury [56]. Animal studies have shown that the inhibition of selectin-carbohydrate interactions can alleviate these inflammatory responses. 

Recently a form of type 1 fimbriae has been described which, in addition to binding carbohydrates, interacts also with non-glycosylated regions of proteins in a mannose-inhibitable manner [51]. It is not clear whether this interaction occurs via the carbohydrate binding site proper and how it is inhibited by mannose. The difference between the two... 

Carbohydrate-protein interactions are usually highly speeifie. As with carbohydrate-carbohydrate interactions, multivalence is essential, beeause multiple interactions between carbohydrates and proteins are necessary to aehieve strong binding or enhanced inhibition. In pursuit of synthetic targets where carbohydrates are multiply displayed over suitable scaffolds, a number of model systems have been used to study multivalent interactions between carbohydrates and proteins.GNPs have also been used in this field, and the results have been reviewed. ... 

Procyanidins have been considered antinutritional compounds because they can interact with proteins, starch, essential amino acids, and carbohydrates and inhibit certain enzymes [121-123]. This binding depends on the degree of polymerization the larger molecules tend to bind more efficiently [7]. However, at the dose present in cocoa no adverse effect has been observed [124, 125]. In addition, the level of flavonoids required to induce mutations and cytotoxicity may not be physiologically achievable through dietary sources however the use of flavonoid supplements could result in... 

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