Carbohydrates, and cyclodextrins

This result, and others [55,103,1041 from model calculations, gave an early theoretical basis for understanding the predominance of finite and infinite chains of hydrogen bonds in the carbohydrate and cyclodextrin crystal structures in which there is a uniform donor-acceptor direction, as in 4,... 

Abstract Carbohydrates have been investigated and developed as delivery vehicles for shuttling nucleic acids into cells. In this review, we present the state of the art in carbohydrate-based polymeric vehicles for nucleic acid delivery, with the focus on the recent successes in preclinical models, both in vitro and in vivo. Polymeric scaffolds based on the natural polysaccharides chitosan, hyaluronan, pullulan, dextran, and schizophyllan each have unique properties and potential for modification, and these results are discussed with the focus on facile synthetic routes and favorable performance in biological systems. Many of these carbohydrates have been used to develop alternative types of biomaterials for nucleic acid delivery to typical polyplexes, and these novel materials are discussed. Also presented are polymeric vehicles that incorporate copolymerized carbohydrates into polymer backbones based on polyethylenimine and polylysine and their effect on transfection and biocompatibility. Unique scaffolds, such as clusters and polymers based on cyclodextrin (CD), are also discussed, with the focus on recent successes in vivo and in the clinic. These results are presented with the emphasis on the role of carbohydrate and charge on transfection. Use of carbohydrates as molecular recognition ligands for cell-type specific dehvery is also briefly... 

A molecular dynamics simulation of the crystal structures of a-cyclodextrin hexahydrate and / -cyclodextrin dodecahydrate was more successful. In both hydrates, the carbohydrate atomic positions and two third of the water positions were reproduced within the experimental accuracy, and most of the O-H 0 hydrogen bonds that had been determined by neutron diffraction studies (Part III, Chap. 18) also showed up in the simulation [360, 361]. 

Hydrogen-bonding patterns in crystal structures of the cydodextrins and the simpler carbohydrates differ. The infinite, homodromic chains are common both in the low molecular-weight carbohydrates and in the cydodextrins. The principal difference lies in the frequency of occurrence of the homodromic and antidromic cycles, which are common in the cyclodextrin crystal structures and rare in the mono-, di-, and trisaccharides. The cyclic patterns are the rule in the clathrate hydrates and in the ices. From this point of view, the hydrogen-bonding patterns of the hydrated cydodextrins lie between those of the simpler hydrated carbohydrates and those of the hydrate inclusion compounds, discussed in Part IV, Chapter 21. 

Carbohydrates - Starches and cyclodextrins Aqueous Inclusion complexes... 

Long-chain aliphatic olefins give only insufficient conversion to the acids due to low solubility and isomerization side reactions. In order to overcome these problems the effect of co-solvents and chemically modified /i-cyclodextrins as additives was investigated for the hydrocarboxylation of 1-decene [23], Without such a promoter, conversion and acid selectivity are low, 10% and 20% respectively. Addition of co-solvents significantly increases conversion, but does not reduce the isomerization. In contrast, the addition of dimethyl-/i-cyclodextrin increased conversion and induced 90% selectivity toward the acids. This effect is rationalized by a host/ guest complex of the cyclic carbohydrate and the olefin which prevents isomerization of the double bond. This pronounced chemoselectivity effect of cyclodextrins is also observed in the hydroformylation and the Wacker oxidation of water-insoluble olefins [24, 25]. More recent studies of the biphasic hydrocarboxylation include the reaction of vinyl aromatic compounds to the isomeric arylpropanoic acids [29, 30], and of small, sparingly water-soluble alkenes such as propene [31]. 

Cyclodextrin glycosyltransferase can use a variety of carbohydrates and other compounds as acceptors in the reactions. The synthesis of a number of... 

Starch-Modifying Enzymes Starch is one of the most abundant carbohydrates in terrestrial plants and the most important polysaccharide used by humankind. This polymer is normally processed and used in a variety of products such as starch hydrolysates, starch or maltodextrin derivatives, fructose, glucose syrups, and cyclodextrins [148, 149]. In addition, starch is widely used as a raw material in the paper industry, in polyol production, and as economic substrate for many microbial fermentations [149]. Starch consists of a large number of glucose units that can be linearly attached as hehcal amylose [ 99% a-(l-4) and 1% a-(l-6) bonds] or branched as amylopectin [ 95% a-(l-4) and 5% a-(l-6) bonds] [69]. In nature, four types of starch-converting enzymes exist (i) endoamylases (ii) exoamylases (iii) debranching enzymes and (iv) transferases. 

Polyplexes are formed from many cationic polymers such as histones, PEI, dendrimers (pDMAEM) or carbohydrate-based polymers such as chitosan and cyclodextrin. Polyplexes are smaller in size than lipoplexes, which is a major physicochemical property for gene delivery, especially in vivoJ... 

Recently many studies have been made in connection with the interaction between carbohydrate degrading enzymes and cyclodextrins (1-9). 

Highly oxidizable oils such as fish oils can be protected by a process known as microencapsulation, which coats the oil with a matrix of protein (gelatin, casein), carbohydrates (starch, cellulose, carboxymethylcellulose or cellulose derivatives) and lecithin. Microencapsulation provides protection against oxidation and imparts oxidative stability. The use of carboxymethylcellulose and cyclodextrins as coatings is claimed to provide better protection of oils by improved oxygen barrier properties. For special applications as nutritional supplements, fish oils enriched in n-3 PUFA are microencapsulated, in the presence of antioxidants, into a powder that is relatively stable at ambient temperatures. However, encapsulated fish oils can impart undesirable fishy taste when incorporated into food emulsions. More research and development is needed to evaluate potential applications and benefits of active packaging to increase the shelf life of fish oils and other highly oxidizable oils in foods. 

Even pseudopolyrotaxanes and polyrotaxanes of cyclo-dextrins threaded onto linear polymer chains have been employed to display carbohydrates and achieve dynamic multivalent glycomimetics. These beads-on-a-string have been adapted for the multivalent display of lactosides in order to bind to galectin-1. The cyclodextrins are able to spin around the axes of the polymer chains as well as move back and forth along the polymer backbones. Thus, spatial mismatches between the ligand and the receptor can be eliminated by adaptable presentation of epitopes on account of the dynamic flexibiUty of the pseudopolyrotaxane architecture. ... 

Previous interest in the antitumor activity of fig (Ficus carica L.) fruit led to the isolation of benzaldehyde as a major active component (22). Its carcinostatic effect was attributed to selective inhibition of the uptake of nucleosides and carbohydrates, and the reduction of intracellular adenosine 5 -triphosphate level (23) However, benzaldehyde is an oilly liquid and only sparingly water soluble. Its instability in air and light presented considerable problems in the delivery and formulatioa Takeuchi et al (24) first prepared the complex with a-, p- and y-cyclodextrin. More importantly, the x-ray structure of a-cyclodextrin-ben dehyde 1 1 complex was subsequently determined (22). providing a woiking basis for uncovering its structure in solution. 

Karlson, L., Thuresson, K. and Lindman, B. (2002) A rheological investigation of the complex formation between hydrophobicaUy modified ethyl (hydroxy ethyl) cellulose and cyclodextrin. Carbohydr. Polym., 50 (3), 219-226. 

Various chemical species influence the rates of hydrolysis of penicillins, e.g. metal ions (Cu >Zn >Ni Co ) (80JCS(P2)1725), carbohydrates (78MI51101), certain amine-containing catechol derivatives (69JPS1102) and /3-cyclodextrin (71JA767). Some of these even show some of the characteristics of enzyme-catalyzed hydrolyses. 

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