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(12) United States Patent (10) Patent No.: US 9,567,346 B2 Ying Et Al

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(12) United States Patent (10) Patent No.: US 9,567,346 B2 Ying Et Al USOO956,7346B2 (12) United States Patent (10) Patent No.: US 9,567,346 B2 Ying et al. (45) Date of Patent: Feb. 14, 2017 (54) BOTIN DERVATIVES 2008/0076909 A1 3/2008 Schroeder 2008/0255004 A1 10, 2008 Neurauter et al. (75) Inventors: Lai-Qiang Ying, Eugene, OR (US); 2015,0072396 A1* 3, 2015 Gee ...................... CO7D 213.78 Bruce Branchaud, Eugene, OR (US); 435.188 Yu-Zhong Zhang, Eugene, OR (US); FOREIGN PATENT DOCUMENTS Stephen Yue, Eugene, OR (US) EP OO94776 11, 1983 (73) Assignee: LIFE TECHNOLOGIES WO WO-2009, O42544 A1 * 4, 2009 CORPORATION, Carlsbad, CA (US) OTHER PUBLICATIONS (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 Flaster et al., CA 96:122496, 1982. ck Chemical Abstracts Registry No. 258842-82-9, indexed in the U.S.C. 154(b) by 0 days. Registry file on STN CAS Online Mar. 9, 2000.* Ogita et al., Biochemistry, 1988. 27(21), pp. 8028-8033.* (21) Appl. No.: 13/881,518 Griffiths et al., CA 133:100420, 2000.* Raster et al., Journal of Heterocyclic Chemistry, (1981), 18(7), pp. (22) PCT Fed: Oct. 28, 2011 1425-1436. Slavoff et al., Journal of the American Chemical Society, 2008, (86). PCT No.: PCT/US2O11AO584S5 130(4), pp. 1160-1162.* S 371 (c)(1), Finn et al., Bioorganic Chemistry, 1995, 23(2), pp. 152-168.* Sachon et al., FEBS Letters, 2003, 544(1-3), pp. 45-49.* (2), (4) Date: Sep. 26, 2013 Sachon et al., Chemical Abstract 139:160249, 2003.* National Center for Biotechnology Information. PubChem Com (87) PCT Pub. No.: WO2012/058635 pound Database; CID=10448239, http://pubchem.ncbi.nlm.nih.gov/ PCT Pub. Date: May 3, 2012 Summary/summary.cgi?cid=10448239 (create date Oct. 25, 2006).* National Center for Biotechnology Information. PubChem Com (65) Prior Publication Data pound Database; CID=10335693, http://pubchem.ncbi.nlm.nih.gov/ Summary/summary.cgi?cid=10335693 (create date Oct. 25, 2006).* US 2014/OO11255 A1 Jan. 9, 2014 National Center for Biotechnology Information. PubChem Com pound Database; CID=23264086, http://pubchem.ncbi.nlm.nih.gov/ Summary/summary.cgi?cid=23264086 (create date Dec. 5, 2007).* Related U.S. Application Data National Center for Biotechnology Information. PubChem Com (60) Provisional application No. 61/408,210, filed on Oct. pound Database; CID-254 91102, http://pubchem.ncbi.nlm.nih.gov/ 29, 2010, provisional application No. 61f495, O70 Summary/summary.cgi?cid=25491102 (create date May 27, 2009).* filed on Jun. 9, 2011, provisional application No. Nationalauonal UenterCenter forIor BiotechnolSlotechnology InfInTormation tion. PubChem ComO. 61/501,500, filed on Jun. 27, 2011, provisional poundd Database;LuaLabase CID=25133576, http://pubchem.ncbi.nlm.nih.gov/tp://pubchem.ncbi.nlm.nih.gov Summary/summary.cgi?cid=25133576 (create date Jan. 19, 2009).* application No. 61/510,949, filed on Jul. 22, 2011. National Center for Biotechnology Information. PubChem Com pound Database; CID=83863, http://pubchem.ncbi.nlm.nih.gov/ (51) 25 toso (2006.01) Summary/summary.cgi?cid=83863 (create date Jul. 19, 2005).* C8B 37/00 (2006.015 Field, Journal of Organic Chemistry (1978), 43(6), pp. 1084-1085.* GOIN 33/532 (2006.015 McCormick, CA 72:74989, 1970.* GOIN 33/543 (200 6,015 McCormick, Proceedings of the Society for Experimental Biology GOIN 33/58 (2006.015 and Medicine, (1969), 132(2), pp. 502-504.* (52) U.S. Cl Lavielle et al., Journal of the American Chemical Society, Mar. 1, AV e. we 1978, 100(5), pp. 1558-1563.* CPC ............. C07D 495/04 (2013.01); C08B 37/00 Bodanszky(5), et al.,pp Journal of the American Chemical Society, 1977. (2013.01); G0IN 33/532 (2013.01); G0IN 99(1), pp. 235-239.* 33/54353 (2013.01); G0IN 33/58 (2013.01); Kumar et al., Nucleosides & Nucleotides, 1996, 15(7 & 8), pp. G0IN 33/582 (2013.01) 1263-1273. (58) Field of Classification Search EP 1183.7225.9, “European Search Report”, 13 pgs, Jul. 15, 2014. CPC .................................................... COP9 Miyamoto, S. et al., “Absolute and Relative Binding Free Energy USPC ............................................ 583.0.1, 30.7 Calculations of the Interaction of Biotin and Its Analogs with See application file for complete search history. Streptavidin Using Molecular Dynamics/Free Energy Perturbation Approaches'. PROTEINS: Structure, Function, and Genetics, vol. (56) References Cited 16, 1993, pp. 226-245. U.S. PATENT DOCUMENTS (Continued) 4,529,587 A * 7/1985 Green .......................... 424.70.8 Primary Examiner — Laura L. Stockton 4,584, 191 A * 4, 1986 Hostettler et al. ........... 424.70.1 6,525,203 B1 2/2003 Tino (57) ABSTRACT 7,141,676 B1 * 1 1/2006 Wilbur et al. ............. 548,303.7 Biotin derivatives, methods of using the biotin derivatives 2005/0101485 A1 5, 2005 Hoffman et al. and kits comprising the biotin derivatives. 2006/0051811 A1 3, 2006 Cotton 2006/0178507 A1* 8/2006 Berry et al. ................. 536,25.3 12 Claims, 8 Drawing Sheets US 9,567,346 B2 Page 2 (56) References Cited Hirsch , et al., “Easily reversible desthiobiotin binding to OTHER PUBLICATIONS Streptavidin, avidin, and other biotin-binding proteins: uses for protein labeling, detection, and isolation'. Analytical Biochemistry, Wang, J. et al., “Ranking Ligand Binding Affinities With Avidin: A vol. 308, No. 2002, 343-357. Molecular Dynamics-Based Interaction Energy Study”. PRO TEINS: Structure, Function, and Genetics, vol. 34, 1999, pp. 69-81. “PCT/US2011/058455”, International Search Report and Written Opinion mailed, Apr. 3, 2012. * cited by examiner U.S. Patent Feb. 14, 2017 Sheet 1 of 8 US 9,567,346 B2 FIG. U.S. Patent Feb. 14, 2017 Sheet 2 of 8 US 9,567,346 B2 B 100% Cell depletion 80/o Cell yield 99% purity m) -- Sny biotin C FG, 2. U.S. Patent Feb. 14, 2017 Sheet 4 of 8 US 9,567,346 B2 FIG. 4 U.S. Patent Feb. 14, 2017 Sheet S of 8 US 9,567,346 B2 treated {4} FGS U.S. Patent Feb. 14, 2017 Sheet 6 of 8 US 9,567,346 B2 N3'-Etity bioti aikyne Biatin alkyne 8 F.G. 6 U.S. Patent Feb. 14, 2017 Sheet 7 of 8 US 9,567,346 B2 Ceixeires cubation iss each asfer teads-free ces?--~~~~x~~~~. ceim Citat begiet 3. Reese recor-grooverror 8.83-8: sea-a-a-a-a-a- s : 8: 35 Before isolation After depletion After release F.G. 7 US 9,567,346 B2 1. 2 BIOTIN DERVATIVES In some embodiments, if R is H. R. is a derivative group and if R is H. R. is a derivative group. In some embodi This application is a U.S. National Stage Application of ments, R is a derivative group. In some embodiments, R PCT Application Serial No. PCT/US2011/058455, filed Oct. comprises 1 to 8 carbon atoms, 1 to 6 carbon atoms, or 1 to 28, 2011, which claims the benefit of priority to U.S. 5 Application No. 61/408,210, filed Oct. 29, 2010, 61/495, 3 carbon atoms. In some embodiments, R is a derivative 070, filed Jun. 9, 2011, 61/501,500, filed Jun. 27, 2011, and group. In some embodiments, R comprises 1 to 8 carbon 61/510,949, filed Jul. 22, 2011. atoms, 1 to 6 carbon atoms, or 1 to 3 carbon atoms. In some embodiments, X is O. In some embodiments, X is S. In some BACKGROUND embodiments, Y is absent. In some embodiments, Y is O. 10 In some embodiments, a biotin derivative is provided that The interaction between biotin and avidin or streptavidin is considered to be practically irreversible. Biotin has a has the formula: affinity constant, or K, for avidin of about 10 M. While the interaction provides an excellent means for capturing biotin-containing entities, releasing those entities once cap 15 (II) tured requires very harsh conditions, such as a strong acid, detergent, and/or high temperature. Such conditions include, for example, boiling in high salt; formamide and EDTA RN l NR heated to 94° C.; 6 M guanidine, pH 1.5; and heating to at least 65° C. in the presence of salt, SDS, and EDTA. Such conditions are generally not suitable for purification of proteins or viable cells or viruses. N-n-r NR, O SUMMARY 25 The inventors have developed biotin derivatives that have wherein: reduced affinity for streptavidin. Thus, in some embodi X is S or O: ments, the biotin derivatives can be separated from Strepta vidin under less harsh conditions than are required for biotin. R is selected from H and a derivative group; Accordingly, in some embodiments, the biotin derivatives 30 R is selected from H and a derivative group: are better suited for applications in which it would be L is absent or is a linker, desirable to dissociate the biotin derivative from streptavidin under less harsh conditions, such as to maintain the struc R is selected from —OR or —COOR, a reactive group, tural integrity and/or viability of the moiety attached to the a protein, a peptide, an amino acid, a dextran, a monosac biotin derivative. 35 charide, a disaccharide, a trisaccharide, an oligosaccharide, In some embodiments, biotin derivatives are provided. In a polysaccharide, a hormone, a lipopolysaccharide, a some embodiments, a biotin derivative is provided that has nucleotide, an oligonucleotide, a small molecule, a cell, a the formula: microplate, and a microparticle; R is selected from H and a derivative group; 40 wherein at least one of R and R is H. X (I) In some embodiments, if R is H. R. is a derivative group, and if R is H. R. is a derivative group. In some embodi s ments, R is a derivative group.
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