Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Patent
1994-02-07
1996-07-02
Rollins, John W.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
435 73, 435 74, 435101, 435200, 53612313, 5361231, C12P 1912, C12P 1964
Patent
active
055321470
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a procedure for synthesis of derivatives of galactose containing carbohydrates and of glucose containing carbohydrates which are suitable for further synthesis of, for example, biological receptor structures, such as blood group determinants, or of other derivatives which can be used directly in medical/diagnostical applications.
Carbohydrates have a central function in living organisms, in the metabolism, as an energy source, for protection against the environment, as biological markers, as receptor substances and as antigenic determinants. The oligosaccharide part of glycoproteins and glycolipids are important in vivo (Biology of Carbohydrates, vol. 2, Ginsburg et al., Wiley, New York, 1984; The Glycoconjugates, vol. I-V, Academic Press, New York; S. Hakomori, Ann. Rev. Biochem., vol. 50, pp. 733-64; Feizi, Nature, pp. 314, 1985; S. Hakomori, Chemistry and Physics of Lipids, vol. 42, pp. 209-33). Among other things it was found that localisation, immunogenicity and degradation of glycoproteins; antigens); pathogens, proteins, hormones, toxins and during cell-cell interactions; oligosaccharides have been found to be cancer-associated antigenic determinants; carbohydrate part of the glycoconjugate is required for full biological activity (e.g. receptor activity).
Oligosaccharide derivatives which contain one or more modified/derivatised monosaccharide units, for example deoxy-, phospho-, sulphate-, derivatised amino- or thio groups, are of high interest for pharmaceutical or diagnostic applications of carbohydrates, to modify the metabolism of the substance and/or to increase the biological effect of the natural substance.
Carbohydrate derivatives are also used in general as synthetic intermediates to achieve selective organic-chemical synthesis of carbohydrates (see e.g. Binkley: Modern Carbohydrate Chemistry, Marcel Dekker, New York, 1988, with references). Selective chemical syntheses of carbohydrates require advanced protection group chemistry with many synthetic steps, inter alia because the syntheses of selectively modified carbohydrate intermediates are complicated. Efficient techniques for preparation of such carbohydrate intermediates are thus desired.
The present invention describes a process which makes possible a drastically simplified synthesis of derivatised/modified di-, tri-, and higher oligosaccharides. Carbohydrate derivatives which required several reaction steps to synthesise with previous methods, can, with the method according to the present invention, now be obtained with only one reaction step and with absolute stereospecificity, which also is different from chemical methods, where more or less poisonous reagents, e.g. Ag-triflate or mercury cyanide, have been used and where the desired .alpha.- or .beta.-isomer was obtained together with the undesired stereoisomer.
The synthetic method according to the invention includes at least one process characterised by that a glycosidase (EC 3.2) is used to catalyse an equilibrium or a transglycosylation reaction between an acceptor substance, which consists of either a galactose derivative or a glucose derivative, and a glycosyl donor, which is a monosaccharide, oligosaccharide or a glycoside, and that the product is used for continued synthesis and/or is isolated from the product mixture. In this way one obtains, according to the invention, stereospecific synthesis of di-, tri-, or higher oligosaccharide derivatives, which can be used directly, or after further synthesis, for a number of various applications, e.g. for pharmaceutical/medical/diagnostical studies, for applications in therapy, diagnostics, as additives in cosmetics or in food, for modification of separation material, affinity chromatography, modification of amino acids, peptides, proteins, fatty acids, lipids, enzymes, recombinant proteins.
In the synthesis according to the invention, the capacity of glycosidases to form stereospecific glycosidic linkages between a glycosyl donor (DOR in the scheme below, where D symbolises the transferred carb
REFERENCES:
patent: 4918009 (1990-04-01), Nilsson
patent: 5246080 (1993-09-01), Nilsson
Prats Francisco C.
Rollins John W.
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