Inclusion complexes with proteins

Molecular Interactions. Various polysaccharides readily associate with other substances, including bile acids and cholesterol, proteins, small organic molecules, inorganic salts, and ions. Anionic polysaccharides form salts and chelate complexes with cations some neutral polysaccharides form complexes with inorganic salts and some interactions are stmcture specific. Starch amylose and the linear branches of amylopectin form inclusion complexes with several classes of polar molecules, including fatty acids, glycerides, alcohols, esters, ketones, and iodine/iodide. The absorbed molecule occupies the cavity of the amylose helix, which has the capacity to expand somewhat to accommodate larger molecules. The starch—Hpid complex is important in food systems. Whether similar inclusion complexes can form with any of the dietary fiber components is not known. 

Inclusion complexes of amylose are rather well defined, and a consistent theory of such complexes is available that explains amylose complexes with iodine, fatty acids, alcohols, and other guest molecules.4,5 This subject is surveyed in this article because of the growing interest and importance of such complexes in pharmacology and in the food industry. It is probable that starch in its biological sources (tubers, granules) exists in the form of native complexes with proteins, lipids, mineral salts, and water. 

Several organic compounds either change the color of the complex or eliminate color altogether. Color disappears under treatment with egg albumen and several proteins, an effect caused by the formation of inclusion complexes with the proteins. Among a-amino acids, only tyrosine exhibited such behavior. Furfural also decomposes the blue complex and epinephrine... 

Starch in plants is accompanied by water, metal ions, lipids, proteins, sterols (such as saponins), and alkaloids (as in such exotic plants as Diascoracea).649 Several of these components can be washed out by the isolation of starch, some of them are extractable with organic solvents, and some are volatized by steam treatment. With the exception of metal ions (preceding article, p. 263), the foregoing components form physical mixtures with starch and do not chemically bond with either amylose or amylopectin. Therefore, one may assume that amylose and amylopectin form inclusion complexes with organic components that are similar to those mentioned in the preceding article. 

Formation of inclusion complexes of starch becomes a more common method of protecting some volatile, as well air-sensitive, food components (microencapsulation). Such complexes are essential for food texturization and overall stabilization. Cationic starches are used as detergents and cellulose pulp components, whereas anionic starches readily form complexes with proteins (Schmitt et al 1998). The latter are attempted in utilization as biodegradable plastics and meat substitutes. 

Many interactions are of a pure chemical nature and may result from the presence of aldehydes and their reactivity toward amino and thiol groups of proteins. Another frequently occurring type of interaction is the formation of hydrogen bonds between food compounds and polar flavor components such as alcohols. Starch, starch-derived maltodextrins, and (3-cyclodextrin are able to form inclusion complexes with many flavor components. Many other interactions, although of great influence on flavor perception, are of a physical nature and therefore not mentioned in this chapter. 

The approach using cyclodextrin as a binding site has also been developed. Cyclodextrins are widely utilized in biomimetic chemistry as simple models for an enzyme because they have the ability to form inclusion complexes with a variety of molecules and because they have catalytic activity toward some reactions. Kojima et al. (1980, 1981) reported the acceleration in the reduction of ninhydrin and some dyes by a 1,4-dihydronicotinamide attached to 3 Cyclodextrin. Saturation kinetics similar to enzymatic reactions were observed here, which indicates that the reduction proceeds through a complex. Since the cavity of the cyclodextrin molecule has a chiral environment due to the asymmetry of D-glucose units, these chiralities are expected to be effective for the induction of asymmetry into the substrate. Asymmetric reduction with NAD(P)H models of this type, however, has not been reported. Asymmetric reduction by a 1,4-dihydronicotinamide derivative took place in an aqueous solution of cyclodextrin (Baba et al. 1978), although the optical yield from the reduction was quite low. Trifluoromethyl aryl ketones were reduced by PNAH in 1.1 to 5.8 % e.e. in the presence of 3-cyclodextrin. Sodium borohydride works as well (Table 18). In addition to cyclodextrin, Baba et al. also found that the asymmetric reductions can be accomplished in the presence of bovine serum albumin (BSA) which is a carrier protein in plasma. 

Cyclodextrins have had valuable industrial uses for a considerable time, particularly as agents to bind or release volatile molecules. Accurate predictions concerning the selectivity and stability of cyclodextrin-guest complexes are therefore of considerable interest both academically and practically." MD was used to simulate cyclodextrin hydrates" as a test of the applicability of the GROMOS program package to systems beyond proteins and nucleic acids. Other early MD simulations focused on interactions with guests such as enantiomers of methyl-2-chloropropionate. Comparisons between calculated thermodynamic properties for complexes formed by O -cyclodextrin with para-substituted phenols and the results of MM simulations led to improvements in force fields that described the interactions. MM2 simulations were used to support NMR data for the -cyclodextrin inclusion complex with benzoic acid. " The well-known catalytic effect of cyclodextrins has been modeled. For example, the relative rate increase of hydrolysis of S over R phenyl ester stereoisomers in the presence of -cyclodextrin... 

Dihydroquercetin (taxifolin, DHQ) is a natural flavonoid, which possesses antioxidant activity and other pharmacological properties (anti-inflammatory, anti-atherosclerotic, etc.). Dihydroquercetin is hydrophobic compound, that s why it can t be administered intravenously, also its oral bioavailability is reduced. Recently, many new dihydroquercetin derivatives were synthesized, including water-soluble forms (cyclodextrin inclusion complexes with dihydroquercetin derivatives). In addition to the protective effect of antioxidants against lipid peroxidation, increasing attention is paid to the possibilities of antioxidants including dihydroquercetin to prevent an oxidation of proteins. Fibrinogen is more susceptible to oxidation than most other plasma proteins. 

On the other hand, as biological molecules become larger their tendency to be associated with water molecules, metal ions, and other materials increases. Crystalline proteins, for example, routinely contain 27-65 % of the solvent used for their crystallisation 183). Such associated materials may be difficult to locate by crystallography and it may become a question of terminology whether such molecules should be regarded as inclusion complexes, non-specific aggregates, or merely contaminated biomolecules. 

The requirement of multifunctional peptide complexes is perhaps most obvious for the development of subunit peptide vaccines. Successful immunizations with peptide antigens cannot be achieved without the inclusion of a bystander T-helper cell determinant in the chemical entity (4) or in the immunizing cocktail (5). For outbred animals and humans, multiple peptide epitopes, representing determinants of more than one major histocompatibility complex (MHC) proteins, are used to overcome subunit vaccine unresponsiveness, and this also improves antigen presentation in inbred animals (6). 

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