Biomaterial Database

Concepts for improved regioselective placement of O-sulfo, N-sulfo, N-acetyl, and N-carboxymethyl groups in chitosan derivatives. 2001

H Baumann, and V Faust

ITMC, Macromolecular Chemistry and Textile Chemistry, Hemocompatible and Biocompatible Biomaterials, University of Technology Aachen, Germany. baumann@rwth-aachen.de

In the present paper a new strategy has been studied to introduce solely or in combination N-sulfo, O-sulfo, N-acetyl, and N-carboxymethyl groups into chitosan with highest possible regioselectivity and completeness and defined distribution along the polymer chain. The aim was to generate compounds having lowest toxicity for determining the pharmacological structure function relationships among different backbone structures and differently arranged functional groups compared to those of heparin and heparan sulfate. The water-soluble starting material, chitosan, with a degree of acetylation (DA) of 0.14 and a molecular weight of 29 kD, allows one to apply most of the known reactions of chitosan as well as some reactions of heparin chemistry successfully and with improved regioselectivity and completeness. On the other hand, a number of these reactions were not successful by application to water-soluble high-molecular-weight chitosan (DA 0.45 and 150 kD). The starting material showed statistical N-acetyl (N-Ac) distribution along the polymer chain according to the rules of Bernoulli, with highest abundance of the GlcNAc-GlcNAc diad along with a lower abundance of triads, tetrads, and pentads. The space between the N-Ac groups was filled up in homogeneous reactions by N-sulfo and/or N-carboxymethyl groups, which also resulted in a Bernoulli statistical distribution. The N-substitution reaction showed highest regioselectivity and completeness with up to three combined different functional groups. The regioselectivity of the 3-O-sulfo groups was improved by regioselective 6-desulfation of nearly completely sulfated 3,6-di-O-sulfochitosan. By means of desulfation reactions, all of the possible intermediate sulfated products are possible. 6-O-Sulfo groups can also be introduced with highest regioselectivity and completeness, and a number of partially 6-desulfated products are possible.

UI	MeSH Term	Description	Entries
D007202	Indicators and Reagents	Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)	Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D008970	Molecular Weight	The sum of the weight of all the atoms in a molecule.	Molecular Weights,Weight, Molecular,Weights, Molecular
D002236	Carbohydrate Conformation	The characteristic 3-dimensional shape of a carbohydrate.	Carbohydrate Linkage,Carbohydrate Conformations,Carbohydrate Linkages,Conformation, Carbohydrate,Conformations, Carbohydrate,Linkage, Carbohydrate,Linkages, Carbohydrate
D002240	Carbohydrate Sequence	The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS.	Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D002686	Chitin	A linear polysaccharide of beta-1->4 linked units of ACETYLGLUCOSAMINE. It is the second most abundant biopolymer on earth, found especially in INSECTS and FUNGI. When deacetylated it is called CHITOSAN.
D003386	Brachyura	An infraorder of chiefly marine, largely carnivorous CRUSTACEA, in the order DECAPODA, including the genera Cancer, Uca, and Callinectes.	Blue Crab,Callinectes sapidus,Carcinus maenas,Crab, Blue,Crab, Common Shore,Crab, Green,Crabs, Short-Tailed,Crabs, True,Green Crab,Uca,Common Shore Crab,European Shore Crab,Blue Crabs,Brachyuras,Carcinus maena,Common Shore Crabs,Crab, European Shore,Crab, Short-Tailed,Crab, True,Crabs, Blue,Crabs, Common Shore,Crabs, Green,Crabs, Short Tailed,Green Crabs,Shore Crab, Common,Shore Crab, European,Shore Crabs, Common,Short-Tailed Crab,Short-Tailed Crabs,True Crab,True Crabs,Ucas,maenas, Carcinus
D006493	Heparin	A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.	Heparinic Acid,alpha-Heparin,Heparin Sodium,Liquaemin,Sodium Heparin,Unfractionated Heparin,Heparin, Sodium,Heparin, Unfractionated,alpha Heparin
D006497	Heparitin Sulfate	A heteropolysaccharide that is similar in structure to HEPARIN. It accumulates in individuals with MUCOPOLYSACCHARIDOSIS.	Heparan Sulfate,Sulfate, Heparan,Sulfate, Heparitin
D000085	Acetates	Derivatives of ACETIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxymethane structure.	Acetate,Acetic Acid Esters,Acetic Acids,Acids, Acetic,Esters, Acetic Acid