# US 11,993,627 B2 · Enzymatic synthesis of homogeneous chondroitin sulfate oligosaccharides

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- Number: US 11,993,627 B2
- Document ID: US11993627B2
- Status: Granted
- Kind: B2
- Application number: 16/625,342
- Filed: 2018-07-03
- Published: 2021-10-28
- Granted: 2024-05-28
- Earliest claimed: 2017-07-03
- Assignees: The University of North Carolina at Chapel Hill
- Applicants: The University of North Carolina at Chapel Hill
- Inventors: Jian Liu; Jine Li; Guowei Su
- Web page: https://patentgrep.com/patent/US11993627B2

## CPC

- C07H 3/06: Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
- C07H 1/00: Processes for the preparation of sugar derivatives
- C07H 11/00: Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof (halo-sugars C07H5/02; thio-, seleno-, or telluro-sugars C07H5/08)
- C08B 37/0063: {Glycosaminoglycans or mucopolysaccharides, e.g. keratan sulfate; Derivatives thereof, e.g. fucoidan}
- C08B 37/0069: {Chondroitin-4-sulfate, i.e. chondroitin sulfate A; Dermatan sulfate, i.e. chondroitin sulfate B or beta-heparin; Chondroitin-6-sulfate, i.e. chondroitin sulfate C; Derivatives thereof}
- C12N 9/1048: {Glycosyltransferases (2.4)}
- C12N 9/13: {transferring sulfur containing groups (2.8)}
- C12P 19/26: Preparation of nitrogen-containing carbohydrates
- A61K 31/737: Sulfated polysaccharides, e.g. chondroitin sulfate, dermatan sulfate (A61K31/727 takes precedence)
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12P: FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE {(brewing of beer C12C; producing vinegar C12J; producing specific peptides or proteins C07K; producing enzymes C12N9/00; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; measuring or testing processes involving enzymes or microorganisms C12Q; measuring or testing processes involving nucleic acid amplification reactions C12Q1/6844; fermentation processes to form a food composition, A21 or A23; compounds in general, see the relevant compound class, e.g. C01, C07)}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Methods of synthesizing chondroitin sulfate oligosaccharides are provided. Enzymatic schematic approaches to synthesizing structurally defined homogenous chondroitin sulfate oligosaccharides at high yields are provided. Synthetic chondroitin sulfate oligosaccharides ranging from 3-mers to 15-mers are provided.

## Claims

### Claim 1

A synthetic chondroitin sulfate oligosaccharide, wherein the synthetic chondroitin sulfate oligosaccharide comprises a 4-O-sulfated and/or 6-O-sulfated chondroitin oligosaccharide selected from a chondroitin sulfate D (CS-D) 13-mer, a CS-D 14-mer, and a CS-D 15-mer.

### Claim 2 (depends on 1)

A composition comprising one or more synthetic chondroitin sulfate oligosaccharides of claim 1.

### Claim 3 (depends on 2)

The composition of claim 2, further comprising a pharmaceutically acceptable carrier.

### Claim 4

A synthetic chondroitin sulfate oligosaccharide, wherein the synthetic chondroitin sulfate oligosaccharide comprises a 4-O-sulfated and/or 6-O-sulfated chondroitin oligosaccharide selected from a chondroitin sulfate C (CS-C) or a chondroitin sulfate D (CS-D) and having a size ranging from a 13-mer to a 15-mer, and wherein the synthetic chondroitin sulfate oligosaccharide is an unnatural chondroitin sulfate oligosaccharide, wherein the unnatural chondroitin sulfate oligosaccharide comprises a 6-O-sulfo2-azido galactosamine or a 6-O-sulfo galactosamine residue.

### Claim 5

A synthetic chondroitin sulfate oligosaccha ride, wherein the synthetic chondroitin sulfate oligosaccharide comprises a structure selected from the group consisting of:
where R1=R2=H; R3=NHFTA,
where R1=SO3H; R2=H; R3=NHFTA,
where R1=R2=H; R3=NH2,
where R1=SO3H; R2=H; R3=NH2,
where R1=R2=H; R3=N3, or
where R1=SO3H; R2=H; R3=N3; and
where
R81=SO3H; RD1=RF1=R2=H; and
wherein R is selected from the group consisting of —H, alkyl, substituted alkyl, aryl, and substituted aryl.

### Claim 6 (depends on 5)

The synthetic chondroitin sulfate oligosaccharide of claim 5, wherein the alkyl is —CH3 or —CH2CH3 or the substituted aryl is a p-nitrophenyl group.

### Claim 7 (depends on 5)

A composition comprising one or more synthetic chondroitin sulfate oligosaccharides of claim 5.

### Claim 8 (depends on 7)

The composition of claim 7, further comprising a pharmaceutically acceptable carrier.