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United States Patent (10) Patent No.: US 7,223,570 B2 Aga Et Al

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United States Patent (10) Patent No.: US 7,223,570 B2 Aga Et Al US007223570B2 (12) United States Patent (10) Patent No.: US 7,223,570 B2 Aga et al. (45) Date of Patent: May 29, 2007 (54) BRANCHED CYCLIC TETRASACCHARIDE, 5,763,598 A 6/1998 Hamayasu et al. PROCESS FOR PRODUCING THE SAME, 5,786, 196 A * 7/1998 Cote et al. .................. 435,208 AND USE FOREIGN PATENT DOCUMENTS (75) Inventors: Hajime Aga, Okayama (JP); Takanobu f Higashiyama, Okayama (JP); Hikaru E. 1 . A1 is: Watanabe, Okayama (JP); Tomohiko JP 647s) 1, 1994 Sonoda, Okayama (JP); Michio JP 6-16705 1, 1994 Kubota, Okayama (JP) JP 6-298806 10, 1994 JP 10-25305 1, 1998 (73) Assignee: Kabushiki Kaisha Hayashibara JP 10-304882 11, 1998 Seibutsu Kagaku Kenkyujo, Okayama WO WO 01/90338 A1 11, 2001 (JP) WO WO O2/10361 A1 2/2002 WO WO O2.40659 A1 5, 2002 (*) Notice: Subject to any disclaimer, the term of this WO WO O2/O55708 A1 T 2002 patent is extended or adjusted under 35 U.S.C. 154(b) by 324 days. OTHER PUBLICATIONS (21) Appl. No.: 10/471.377 Biely, P. “Enzymic alpha-galactosylation . " Carbohyd. Res. (2001) vol. 332, pp. 299-303.* (22) PCT Filed: Mar. 8, 2002 Cote, Gregory and Biely, Peter, Enzymically produced cyclic C-1,3- linked and O-1,6-linked oligosaccharides of D-glucose, European (86). PCT No.: PCT/UPO2/O2213 Journal of Biochemistry, vol. 226, (1994), p. 641-648. Sambrook, Joseph and Russell, David, Molecular Cloning. A Labo S 371 (c)(1), ratory Manuel. 3" Edition, (Cold Spring Harbor Laboratory, New (2), (4) Date: Sep. 9, 2003 York), 2001, Chapters 15-17. (87) PCT Pub. No.: WO02/072594 k cited. by examiner Primary Examiner Leigh C. Maier PCT Pub. Date: Sep. 19, 2002 (74) Attorney, Agent, or Firm Browdy and Neimark, PLLC (65) Prior Publication Data US 2004/0236097 A1 Nov. 25, 2004 (57) ABSTRACT (30) Foreign Application Priority Data The object of the present invention is to provide a novel Mar. 9, 2001 (JP) 2001-067282 glycosyl derivative of cyclotetrasaccharide represented by • - s 1- w u way - F · · · · · · · · · · · · · · · · · · · · · · · · · · · · · cyclo->6)-O-D-glucopyranosyl-(1->3)-C-D-glucopyrano (51) Int. Cl. syl-(1->6)-C-D-glucopyranosyl-(1->3)-C-D-glucopyrano C7H 3/06 (2006.01) syl-(1->}, and it is solved by providing a branched cyclotet CI2P 19/18 (2006.01) rasaccharide, wherein one or more hydrogen atoms in the (52) U.S. Cl. .................................... 435/97.536/12312 hydroxyl groups of cyclotetrasaccharide are replaced with (58) Field of Classification Search 536/123.12. an optionally Substituted glycosyl group, with the proviso - - - - - - - - - - - 43 sjo that, when only one hydrogen atom in the C-6 hydroxyl See application file for complete search histo group among the above hydrogen atoms is substituted with pp p ry. an optionally-substituted glycosyl group, the Substituted (56) References Cited glycosyl group is one selected from those excluding D-glu cosyl group. U.S. PATENT DOCUMENTS 5,366,879 A 11/1994 Kitahata et al. 29 Claims, 20 Drawing Sheets U.S. Patent May 29, 2007 Sheet 1 of 20 US 7,223,570 B2 FIG. 1 Retention time (min) U.S. Patent May 29, 2007 Sheet 2 of 20 US 7,223,570 B2 IG. 2 i Shift value (PPM) U.S. Patent May 29, 2007 Sheet 3 of 20 US 7,223,570 B2 FIG. 3 Stift Wallue (PPM) FG. 4. : maen:No.,……!!!!!!!!!!!) Pyle's re's pare starts Shift value (PPV) U.S. Patent May 29, 2007 Sheet 4 of 20 US 7,223,570 B2 FIG. 5 > | -- (i) ; O) - r C tre -- (t. || | gold 'r p- "rrentirjatikshire for - intries-y- Wu- PP, r- T --- 100 90 8O 70 6C Shift value (PPM) FIG. 6 ------ mm. > : rrn rr- i () : I ?9 ; | : alJkr- || swell-appaikish-fly-fristed| seriest, Wei- eys: - PPA, - | OO 9 O 8) - 60 Shift value (PPM) U.S. Patent May 29, 2007 Sheet 5 of 20 US 7,223,570 B2 FIG 7 > - -- 2 (1) : i - > ?. its W. Viview vs. PPM. ---- ---------- 50 OO 90 80 70 Shift value (PPM) U.S. Patent May 29, 2007 Sheet 6 of 20 US 7,223,570 B2 FIG. 8a (a) O C O O6 C OS O C - r to log ar < O - - g C. co Ci ?t -- in0 inc H - 0 < ! O An Estient II e A Fate L93 U.S. Patent May 29, 2007 Sheet 7 of 20 US 7,223,570 B2 FIG. 8b O O O O OB 8 C. C. -- E 9) (Cg s C rr i i Op. \ --- C O& C , (D ---------- 2x - An Suent I e An-else U.S. Patent May 29, 2007 Sheet 8 of 20 US 7,223,570 B2 FLG. 9 |-------- shift value (PPM) FIG. 1 O Shift value (PPV) U.S. Patent May 29, 2007 Sheet 10 of 20 US 7,223,570 B2 F.G. 13 Shift value (PPM) Shift value (PPM) U.S. Patent May 29, 2007 Sheet 11 of 20 US 7,223,570 B2 U.S. Patent May 29, 2007 Sheet 12 of 20 US 7,223,570 B2 FIG. 16 t n c ---- g: s - \ () - O O ar. -- ) C2 (t r 4as --- t" - -- s --- U.S. Patent May 29, 2007 Sheet 13 of 20 US 7,223,570 B2 FIG. 17 ...-------r-|-~~~~~~~~--- ?noe,JJT(I=T6-LIÐTIO()gz GZ---------------------~--~{-~~~()--------.-----···----|—l-………-------1 --~~~~);o– (sdo) An LSU33. UI U.S. Patent May 29, 2007 Sheet 14 of 20 US 7,223,570 B2 FIG. 18 –*~~~~-----,----------—1–---~~~~–– ||||||||| IJJTCInoetro??treaT()z)( } {}?!-------------------+()()-------------------— U.S. Patent May 29, 2007 Sheet 15 of 20 US 7,223,570 B2 FG 19 Û°C)?I ||||||||| ()~º | {}~ | eT6ueUropaoeaJFGI | ()*[]{ U.S. Patent May 29, 2007 Sheet 16 of 20 US 7,223,570 B2 O c. O ? | || | O - c. | C ! s -1 C --- n t - G) - C - is O) C. d E C.) C) C N i l k- -- rism c { C C C) {} - O C) O C c s i. 9. r ( : ) ofureu o nu fei, U.S. Patent May 29, 2007 Sheet 17 of 20 US 7,223,570 B2 FIG. 21 ---------!----;--------± (O)a.L.eure?ul?Ina --- ) e fuguo nube M U.S. Patent May 29, 2007 Sheet 18 of 20 US 7,223,570 B2 FIG. 22 - C) | - s o f s | i f A - -- : - K.) --- - t --- --1 - C. f c s : se -- H (1) O. c Cl \ i | |t f k f - c. A e } / | ! |f l --- c o c C c c frn V3: t C - U.S. Patent May 29, 2007 Sheet 20 of 20 US 7,223,570 B2 FIG. 24 f 5 - c - ) f ? r A f | | t -- -- i l C WW i. -- 3. -. s (g abue up auf!e M. US 7,223,570 B2 1. 2 BRANCHED CYCLIC TETRASACCHARIDE, ride has been expected to be used in different fields similarly PROCESS FOR PRODUCING THE SAME, as in or much more useful than conventional cyclodextrins. AND USE The method of the report, however, may not suitable for an industrial-scale production of cyclotetrasaccharide, because TECHNICAL FIELD alternan used as a starting material is not easily obtainable The present invention relates to a novel branched cyclic and the yield of cyclotetrasaccharide from the material is tetrasaccharide, more particularly, a glycosyl derivative of a insufficient in view of industrial-scale production. cyclic tetrasaccharide represented by the chemical formula The same applicant as the present invention disclosed an of cyclo{->6)-O-D-glucopyranosyl-(1->3)-O-D-glucopyra O-isomaltosyl-transferring enzyme, a novel enzyme which nosyl-(1->6)-O-D-glucopyranosyl-(1->3)-O-D-glucopyra 10 forms cyclotetrasaccharide when acts on a saccharide having nosyl-(1->}, a process for producing the same, and uses a glucose polymerization degree of at least three and having thereof. both an isomaltosyl group at the non-reducing end and the O-1,4-glucosyl bond as a linkage other than the linkage at the BACKGROUND ART non-reducing end (abbreviated as "O-isomaltosylglucosac O- B-, and Y-Cyclodextrins, which consist of 6, 7, and 8 charide” hereinafter) as disclosed in Japanese Patent Appli glucose molecules that are linked each other via the C-14 15 cation No. 149,484/2000, and Japanese Patent Application glucosyl linkage, respectively, have been known as cyclic No 229,557/2000 (International Publication No. WO 01/90, saccharides composed of glucose units. These cyclodextrins 338 A1) applied for based on the above Japanese Patent have been used in a variety of fields due to their advanta Application; and also disclosed an O-isomaltosylglucosac geous inherent properties of non-reducibility, tasteless, charide-forming enzyme, a novel enzyme which forms enclosing hydrophobic materials, etc. There have been being O-isomaltosylglucosaccharide when acts on a maltooli pursued remarkable researches directed to improve proper gosaccharide having a glucose polymerization degree of at ties of cyclodextrins and impart additional new functions least three, as disclosed in Japanese Patent Application No. thereupon. For example, Japanese Patent Kokai Nos. 9,708/ 233,364/2000 and Japanese Patent Application No. 234.937/ 94, 14,789/94, 16,705/94, 298,806/94, and 25.305/98 pro 2000 (International Publication No. WO 02/10.361 A1). posed branched cyclodextrins with different branching 25 applied for based on Japanese Patent Application No.233, structures, which are prepared by coupling a glycosyl group 364/2000. Further, the above applicant proposed a method to such as a glucosyl, galactosyl, mannosyl, glucosaminyl, or produce cyclotetrasaccharide as a main product from starch, N-acetylglucosaminyl group to cyclodextrins; processes for a widely, commonly used material for producing foods by producing the same; and uses thereof.
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