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Effect of trehalose on protein structure

  1. Nishant Kumar Jain,
  2. Ipsita Roy*

Article first published online: 2 DEC 2008

DOI: 10.1002/pro.3

Issue

Protein Science

Protein Science

Volume 18, Issue 1, pages 24–36, January 2009

Additional Information

How to Cite

Jain, N. K. and Roy, I. (2009), Effect of trehalose on protein structure. Protein Science, 18: 24–36. doi: 10.1002/pro.3

Author Information

  1. Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Punjab 160062, India

*Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Punjab 160062, India

Publication History

  1. Issue published online: 16 DEC 2008
  2. Article first published online: 2 DEC 2008
  3. Manuscript Accepted: 23 SEP 2008
  4. Manuscript Revised: 22 SEP 2008
  5. Manuscript Received: 19 JUL 2008

Funded by

  • NIPER, India
  • Department of Biotechnology, Government of India

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References

  • 1
    Ignatova Z, Gierasch LM ( 2006) Inhibition of protein aggregation in vitro and in vivo by a natural osmoprotectant. Proc Natl Acad Sci USA 103: 13357–13361.
  • 2
    Ignatova Z, Gierasch LM ( 2007) Effects of osmolytes on protein folding and aggregation in cells. Methods Enzymol 428: 355–372.
  • 3
    Bordat P, Lerbret A, Demaret J-P, Affouard F, Descamps M ( 2005) Comparative study of trehalose, sucrose and maltose by molecular modelling. Europhys Lett 65: 41–47.
  • 4
    Chen B, Fowler A, Bhowmick S ( 2006) Forced and natural convective drying of trehalose/water thin films: implication in the desiccation preservation of mammalian cells. J Biomech Eng 128: 335–346.
  • 5
    Choi Y, Cho KW, Jeong K, Jung S ( 2006) Molecular dynamic simulations of trehalose as a ‘dynamic reducer’ for solvent water molecules in the hydration shell. Carbohydr Res 341: 1020–1028.
  • 6
    Kilburn D, Townrow S, Muenier V, Richardson R, Alam A, Ubbink J ( 2006) Organization and mobility of water in amorphous and crystalline trehalose. Nat Mater 5: 632–635.
  • 7
    Kuttel MM, Naidoo KJ ( 2005) Ramachandran free-energy surfaces for disaccharides: trehalose, a case study. Carbohydr Res 340: 875–879.
  • 8
    Lerbret A, Bordat P, Affouard F, Descamps M, Migliardo F ( 2005) How homogeneous are the trehalose, maltose, and sucrose water solutions? An insight from molecular dynamics simulations. J Phys Chem B 109: 11046–11057.
  • 9
    Lerbret A, Bordat P, Affouard F, Guinet Y, Hedoux A, Paccou L, Prevost D, Descamps M ( 2005) Influence of homologous disaccharides on the hydrogen-bond network of water: complementary Raman scattering experiments and molecular dynamics simulations. Carbohydr Res 340: 881–887.
  • 10
    Magazú S, Migliardo F, Mondelli C, Vadala M ( 2005) Correlation between bioprotective effectiveness and dynamic properties of trehalose–water, maltose–water and sucrose–water mixtures. Carbohydr Res 340: 2796–2801.
  • 11
    Singh KJ, Roos YJ ( 2006) State transitions and freeze concentration in trehalose-protein-cornstarch mixtures. LWT 39: 930–938.
  • 12
    Carpinelli J, Kraemer R, Agosin E ( 2006) Metabolic engineering of Corynebacterium glutamicum for trehalose over production: role of the TreYZ trehalose biosynthetic pathway. Appl Environ Microbiol 72: 1949–1955.
  • 13
    Duong T, Barrangou R, Russell WM, Klaenhammer TR ( 2006) Characterisation of the tre locus and analysis of trehalose cryoprotection in Lactobacillus acidophilus NCFM. Appl Environ Microbiol 72: 1218–1225.
  • 14
    Elbein AD, Pan YT, Pastuszak I, Carroll D ( 2003) New insights on trehalose: a multifunctional molecule. Glycobiology 13: 17R–27R.
  • 15
    Garg AK, Kim J-K, Owens TG, Ranwala AP, Choi YD, Kochian LV, Wu RJ ( 2002) Trehalose accumulation in rice plants confers high tolerance levels to different abiotic stresses. Proc Natl Acad Sci USA 99: 15898–15903.
  • 16
    Haines AH ( 2006) Non-equivalence ofD- andL-trehalose in stabilizing alkaline phosphatase against freeze-drying and thermal stress. Is chiral recognition involved? Org Biomol Chem 4: 702–706.
  • 17
    Higo A, Katoh H, Ohmori K, Ikeuchi M, Ohmori M ( 2006) The role of a gene cluster for trehalose metabolism in dehydration tolerance of the filamentous cyanobacterium Anabaena sp. PCC 7120. Microbiology 152: 979–987.
  • 18
    Komes D, Lovrić T, Ganić KK, Gracin L ( 2003) Study oftrehalose addition on aroma retention in dehydrated strawberry puree. Food Technol Biotechnol 41: 111–120.
  • 19
    Richards AB, Krakowa S, Dexter LB, Schmid H, Wolterbeek APM, Waalkens-Berendsen DH, Shigoyuki A, Kurimoto M ( 2003) Trehalose: a review of properties, history of use and human tolerance, and results of multiple safety studies. Food Chem Toxicol 40: 871–898.
  • 20
    Higashiyama T ( 2002) Novel functions and applications of trehalose. Pure Appl Chem 74: 1263–1269.
  • 21
    Whatmore AM, Reed RH ( 1990) Determination of turgor pressure in Bacillus subtilis: a possible role for K+ in turgor regulation. J Gen Microbiol 136: 2521–2526.
  • 22
    Kempf B, Bremer E ( 1998) Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments. Arch Microbiol 170: 319–330.
  • 23
    Murphy HN, Stewart GR, Mischenko VV, Apt AS, Harris R, McAlister MS, Driscoll PC, Young DB, Robertson BD ( 2005) The OtsAB pathway is essential for trehalose biosynthesis in Mycobacterium tuberculosis. J Biol Chem 280: 14524–14529.
  • 24
    Rueda B, Miguelez EM, Hardisson C, Manzanal MB ( 2001) Changes in glycogen and trehalose content of Streptomyces brasiliensis during growth in liquid cultures under sporulating and non-sporulating conditions. FEMS Microbiol Lett 194: 181–185.
    Direct Link:
  • 25
    Crowe LM ( 2002) Lessons from nature: the role of sugar in anhydrobiosis. Comp Biochem Phys A 131: 505–513.
  • 26
    Rao V, Gao F, Chen B, Jacobs WR,Jr, Glickman MS ( 2006) Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis-induced inflammation and virulence. J Clin Invest 116: 1660–1667.
  • 27
    Rolland F, Moore B, Sheen J ( 2002) Sugar sensing and signaling in plants. Plant Cell 14: s185–s205.
  • 28
    Eastmond PJ, Graham IA ( 2003) Is trehalose-6-phosphate a regulator of sugar metabolism in plants? J Exp Bot 54: 533–537.
  • 29
    Matsuo T ( 2001) Trehalose protects corneal epithelial cells from death by drying. Br J Ophthalmol 85: 610–612.
  • 30
    Norcia MA ( 2000) Compositions and methods for wound management. Official Gazette US Pat Trademark Office 1232: 424–448.
  • 31
    Arai C, Kohguchi M, Akamatsu S, Arai N, Yoshizane C, Hasegawa N, Hanaya T, Arai S, Ikeda M, Kurimoto M ( 2001) Trehalose suppresses lipopolysaccharide-induced osteoclastogenesis bone marrow in mice. Nutr Res 21: 993–999.
  • 32
    Schwendeman SP, Constantino HR, Gupta RK, Siber GR, Klibanov AM, Langer R ( 1995) Stabilization of tetanus and diphtheria toxoids against moisture-induced aggregation. Proc Natl Acad Sci USA 92: 11234–11238.
  • 33
    Jain NK, Roy I ( 2008) Role of trehalose in moisture-induced aggregation of bovine serum albumin. Eur J Pharm Biopharm 69: 824–834.
  • 34
    Crowe JH, Leslie SM, Crowe LM ( 1994) Is vitrification sufficient to preserve liposomes during freeze-drying? Cryobiology 31: 355–366.
  • 35
    Guo N, Puhlev I, Brown DR, Mansbridge J, Levine F ( 2000) Trehalose expression confers desiccation tolerance on human cells. Nat Biotechnol 18: 168–171.
  • 36
    Sun WQ, Leopold AC ( 1997) Cytoplasmic vitrification and survival of anhydrobiotic organisms. Comp Biochem Physiol 117A: 327–333.
  • 37
    Eroglu A, Russo MJ, Bieganski R, Fowler A, Cheley S, Bayley H, Toner M ( 2000) Intracellular trehalose improves the survival of cryopreserved mammalian cells. Nat Biotechnol 18: 163–167.
  • 38
    Eroglu A, Toner M, Toth TL ( 2002) Beneficial effect of microinjected trehalose on the cryosurvival of human oocytes. Fertil Steril 77: 152–158.
  • 39
    Crowe JH, Hoekstra FA, Nguyen KHN, Crowe LM ( 1996) Is vitrification involved in depression of the phase transition temperature in dry phospholipids? Biochim Biophys Acta 1280: 187–196.
  • 40
    Haddad GG, Ma E ( 2001) Neuronal tolerance to O2 deprivation in drosophila: novel approaches using genetic models. Neuroscientist 7: 538–550.
  • 41
    Chen Q, Haddad GG ( 2004) Role of trehalose phosphate synthase and trehalose during hypoxia: from flies to mammals. J Exp Biol 207: 3125–3129.
  • 42
    Tanaka M, Michida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N ( 2004) Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington's disease. Nat Med 10: 148–154.
  • 43
    Davies JE, Sarkar S, Rubinsztein DC ( 2006) Wild-type PABPN1 is anti-apoptotic and reduces toxicity of the oculopharyngeal muscular dystrophy mutation. Hum Mol Genet 15: 23–31.
  • 44
    Nishizaki Y, Yoshizane C, Toshimori Y, Arai N, Akamatsu S, Hanaya T, Arai S, Ikeda M, Kurimot M ( 2000) Disaccharide-trehalose inhibits bone resorption in ovariectomized mice. Nutr Res 20: 653–664.
  • 45
    Liu R, Barkhordarian H, Emadi S, Park CB, Sierks MR ( 2005) Trehalose differentially inhibits aggregation and neurotoxicity of beta amyloid 40 and 42. Neurobiol Dis 20: 74–81.
  • 46
    Béranger F, Crozet C, Goldsborough A, Lehmann S ( 2008) Trehalose impairs aggregation of PrPSc molecules and protects prion-infected cells against oxidative damage. Biochem Biophys Res Commun 334: 44–48.
  • 47
    Arguelles JC ( 2000) Physiological roles of trehalose in bacteria and yeasts: a comparative analysis. Arch Microbiol 174: 217–224.
  • 48
    Jönsson KI ( 2007) Tardigrades as a potential model organism in space research. Astrobiology 7: 757–766.
  • 49
    Mercer J, Eagles ME, Talbot IC ( 1990) Brush border enzymes in coeliac disease: histochemical evaluation. J Clin Pathol 43: 307–312.
  • 50
    Sasai-Takedatsu M, Taketani S, Nagata N, Furukawa T, Tokunaga R, Kojima T, Kobayashi Y ( 1996) Human trehalase: characterization, localization, and its increase in urine by renal proximal tubular damage. Nephron 73: 179–185.
  • 51
    Bergoz R ( 1971) Trehalose malabsorption causing intolerance to mushrooms. Report of a probable case. Gastroenterology 60: 909–912.
  • 52
    McGarvey OS, Kett VL, Craig DQM ( 2003) An investigation into the crystallisation of α,α-trehalose from the amorphous state. J Phys Chem B 107: 6614–6620.
  • 53
    Nagase H, Endo T, Ueda H, Nakagaki M ( 2002) An anhydrous polymorphic form of trehalose. Carbohydr Res 337: 167–173.
  • 54
    Sussich F, Skopec C, Brady J, Cesaro A ( 2001) Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal? Carbohydr Res 334: 165–176.
  • 55
    Taga T, Senma M, Osaki K ( 1972) The crystal and molecular structure of trehalose dihydrate. Acta Crystallogr B 28: 3258–3263.
    Direct Link:
  • 56
    Jeffrey GA, Nanni R ( 1985) The crystal structure of anhydrous alpha,alpha-trehalose at −150 degrees. Carbohydr Res 137: 21–30.
  • 57
    Nagase H, Endo T, Ueda H, Nakai T ( 2003) Influence of dry conditions on dehydration of α,α-trehalose dihydrate. STP Pharm Sci 13: 269–275.
  • 58
    Crowe JH, Carpenter JF, Crowe LM ( 1998) The role of vitrification in anhydrobiosis. Annu Rev Physiol 60: 73–103.
  • 59
    Crowe JH, Crowe LM, Oliver AE, Tsvetkova N, Wolkers W, Tablin F ( 2001) The trehalose myth revisited: introduction to a symposium on stabilization of cells in the dry state. Cryobiology 43: 89–105.
  • 60
    Green JL, Angell CA ( 1989) Phase relations and vitrification in saccharide-water solutions and the trehalose anomaly. J Phys Chem 93: 2880–2882.
  • 61
    Roos Y ( 1993) Melting and glass transitions of low molecular weight carbohydrates. Carbohydr Res 238: 39–48.
  • 62
    Liu Q, Schmidt RK, Teo B, Karplus PA, Bray JW ( 1997) Molecular dynamics studies of the hydration of α,α-trehalose. J Am Chem Soc 119: 7851–7862.
  • 63
    Chen T, Fowler A, Toner M ( 2000) Literature review: supplemented phase diagram of the trehalose–water binary mixture. Cryobiology 40: 277–282.
  • 64
    Kandror O, DeLeon A, Goldberg AL ( 2002) Trehalose synthesis is induced upon exposure of Escherichia coli to cold and is essential for viability at low temperatures. Proc Natl Acad Sci USA 99: 9727–9732.
  • 65
    Rudolph AS, Crowe JH, Crowe LM ( 1986) Effects of three stabilizing agents—proline, betaine, and trehalose-on membrane phospholipids. Arch Biochem Biophys 245: 134–143.
  • 66
    Branca C, Maccarrone S, Magazú S, Maisano G, Bennington SM, Taylor J ( 2005) Tetrahedral order in homologous disaccharide-water mixtures. J Chem Phys 22: 174513.
  • 67
    Forbes RT, Davis KG, Hindle M, Clarke JG, Maas J ( 1998) Water vapor sorption studies on the physical stability of a series of spray-dried protein/sugar powders for inhalation. J Pharm Sci 87: 1316–1321.
    Direct Link:
  • 68
    Sola-Penna M, Meyer-Fernandes JR ( 1996) Trehalose protects yeast pyrophosphatase against structural and functional damage induced by guanidinium chloride. Z Naturforsch Sect C Biosci 51: 160–164.
  • 69
    Timasheff SN ( 1992) A physicochemical basis for the selection of osmolytes by nature. In: OsmondCB, BolisCL, SomeroGN, editors. Water and life: comparative analysis of water relationships at organic, cellular and molecular levels. Berlin: Springer Verlag, pp 70–86.
  • 70
    Timasheff SN ( 1993) The control of protein stability and association by weak interactions with water: how do solvents affect these processes? Annu Rev Biophys Biomol Struct 22: 67–97.
  • 71
    Kawai H, Sakurai M, Inoue Y, Chujo R, Kobayashi S ( 1992) Hydration of oligosaccharides: anomalous hydration ability of trehalose. Cryobiology 29: 599–606.
  • 72
    Magazú S, Migliardo P, Musolino AM, Sciortino MT ( 1997) α,α-Trehalose-water solutions. 1. Hydration phenomena and anomalies in the acoustic properties. J Phys Chem B 101: 2348–2351.
  • 73
    Elias ME, Elias AM ( 1999) Trehalose + water fragile system: properties and glass transition. J Mol Liq 83: 303–310.
  • 74
    Cho CH, Singh S, Robinson GW ( 1997) Understanding all of water's anomalies with a nonlocal potential. J Chem Phys 107: 7979–7988.
  • 75
    Crowe JH, Crowe LM, Chapman D ( 1984) Preservation of membranes in anhydrobiotic organisms: the role of trehalose. Science 223: 701–703.
  • 76
    Franks F ( 1977) Solvation interactions of proteins in solution. Philos Trans R Soc Lond B Life Sci 278: 33–57.
  • 77
    Liu Q, Brady JW ( 1996) Anisotropic solvent structuring in aqueous sugar solutions. J Am Chem Soc 118: 12276–12286.
  • 78
    Roy I, Sharma A, Gupta MN ( 2004) Obtaining higher transesterification rates with subtilisin Carlsberg in nonaqueous media. Bioorg Med Chem Lett 14: 887–889.
  • 79
    Roy I, Gupta MN ( 2004) Freeze-drying of proteins: some emerging concerns. Biotechnol Appl Biochem 39: 165–177.
    Direct Link:
  • 80
    Carpenter JF, Crowe JH ( 1989) An infrared spectroscopic study of the interactions of carbohydrates with dried proteins. Biochemistry 28: 3916–3922.
  • 81
    Jovanovic N, Bouchard A, Hofland GW, Witkamp GJ, Crommelin DJ, Jiskoot W ( 2006) Distinct effects of sucrose and trehalose on protein stability during supercritical fluid drying and freeze-drying. Eur J Pharm Sci 27: 336–345.
  • 82
    Carpenter JF, Hand SC, Crowe LM, Crowe JH ( 1986) Cryoprotection of phosphofructokinase with organic solutes: characterization of enhanced protection in the presence of divalent cations. Arch Biochem Biophys 250: 505–512.
  • 83
    Sola-Penna M, Ferreira-Pereira A, Lemos AP, Meyer-Fernandes JR ( 1997) Carbohydrate protection of enzyme structure and function against guanidinium chloride treatment depends on the nature of carbohydrate and enzyme. Eur J Biochem 248: 24–29.
    Direct Link:
  • 84
    Clegg JS, Seitz P, Seitz W, Hazlewood CF ( 1982) Cellular responses to extreme water loss: the water-replacement hypothesis. Cryobiology 19: 306–316.
  • 85
    Crowe JH, Oliver AE, Hoekstra FA, Crowe LM ( 1997) Stabilization of dry membranes by mixtures of hydroxyethyl starch and glucose: the role of vitrification. Cryobiology 35: 20–30.
  • 86
    Maury M, Murphy K, Kumar S, Mauerer A, Lee G ( 2005) Spray-drying of proteins: effects of sorbitol and trehalose on aggregation and FT-IR amide I spectrum of an immunoglobulin G. Eur J Pharm Biopharm 59: 251–261.
  • 87
    Sastry GH, Agmon N ( 1997) Trehalose prevents myoglobin collapse and preserves its internal mobility. Biochemistry 36: 7097–7108.
  • 88
    Ragoonanan V, Aksan A ( 2008) Heterogeneity in desiccated solutions: implications for biostabilization. Biophys J 94: 2212–2227.
  • 89
    Pikal MJ, Rigsbee D, Roy ML, Galreath D, Kovach KJ, Wang BS, Carpenter JF, Cicerone MT. Solid state chemistry of proteins: II. The correlation of storage stability of freeze-dried human growth hormone (hGH) with structure and dynamics in the glassy solid. J Pharm Sci 97: 5106–5121.
    Direct Link:
  • 90
    O'Brien J ( 1996) Stability of trehalose, sucrose and glucose to nonenzymatic browning in model systems. J Food Sci 61: 679–682.
    Direct Link:
  • 91
    Tanford C ( 1964) Isothermal unfolding of globular proteins in aqueous urea solutions. J Am Chem Soc 86: 2050–2059.
  • 92
    Auton M, Bolen DW ( 2005) Predicting the energetics of osmolyte-induced protein folding/unfolding. Proc Natl Acad Sci USA 102: 15065–15068.
  • 93
    Auton M, Bolen DW ( 2007) Application of the transfer model to understand how naturally occurring osmolytes affect protein stability. Methods Enzymol 428: 397–418.
  • 94
    Auton M, Bolen DW, Rösgen J. Structural thermodynamics of protein preferential solvation: osmolyte salvation of proteins, aminoacids, and peptides. Proteins 73: 802–813.
    Direct Link:
  • 95
    Wyman J ( 1984) Linkage graphs: a study in the thermodynamics of macromolecules. Q Rev Biophys 17: 453–488.
  • 96
    Chen L-Y, Cabrita GJM, Otzen DE, Melo EP ( 2005) Stabilization of the ribosomal protein S6 by trehalose is counterbalanced by the formation of a putative off-pathway species. J Mol Biol 351: 402–416.
  • 97
    Baptista RP, Pedersen S, Cabrita GJ, Otzen DE, Cabral JM, Melo EP ( 2008) Thermodynamics and mechanism of cutinase stabilization by trehalose. Biopolymers 89: 538–547.
    Direct Link:
  • 98
    Ellis T ( 1987) Proteins as molecular chaperones. Nature 328: 378–379.
  • 99
    Singer MA, Lindquist S ( 1998) Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell 1: 639–648.
  • 100
    Hottiger T, de Virgilio C, Hall MN, Boller T, Wiemken A ( 1994) The role of trehalose synthesis for the acquisition of thermotolerance in yeast. II. Physiological concentrations of trehalose increase the thermal stability of proteins in vitro. Eur J Biochem 219: 187–193.
    Direct Link:
  • 101
    de Virgilio C, Buerckert N, Bell W, Jenoe P, Boller T, Wiemken A ( 1993) Disruption of TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose-6-phosphate and loss of trehalose-6-phosphate phosphatase activity. Eur J Biochem 212: 315–323.
    Direct Link:
  • 102
    Praekelt UM, Meacock MP ( 1990) HSP12, a new small heat shock gene of Saccharomyces cerevisiae: analysis of structure, regulation and function. Mol Gen Genet 223: 97–106.
  • 103
    Smith BJ, Yaffe MP ( 1991) Uncoupling thermotolerance from the induction of heat shock proteins. Proc Natl Acad Sci USA 88: 11091–11094.
  • 104
    Hengge-Aronis R, Klein W, Lange R, Rimmele M, Boos W ( 1991) Trehalose synthesis genes are controlled by the putative sigma factor encoded by rpoS and are involved in stationary-phase thermotolerance in Escherichia coli. J Bacteriol 173: 7918–7924.
  • 105
    Sola-Penn M, Meyer-Fernandes JR ( 1998) Stabilization against thermal inactivation promoted by sugars on enzyme structure and function: why is trehalose more effective than other sugars? Arch Biochem Biophys 360: 10–14.
  • 106
    Benaroudj N, Lee DH, Goldberg AL ( 2001) Trehalose accumulation during cellular stress protects cells and cellular proteins from damage by oxygen radicals. J Biol Chem 276: 24261–24267.
  • 107
    González-Párraga P, Hernández JA, Argüelles JC ( 2003) Role of antioxidant enzymatic defences against oxidative stress H2O2 and the acquisition of oxidative tolerance in Candida albicans. Yeast 20: 1161–1169.
    Direct Link:
  • 108
    Huntington Collaborative Research Group ( 1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971–983.
  • 109
    Ma X, Jamil K, MacRae T, Clegg J, Russell JM, Villeneuve TS, Eulothe M, Sun Y, Crowe JH, Tablin F, Oliver AE ( 2005) A small stress protein acts synergistically with trehalose to confer desiccation tolerance on mammalian cells. Cryobiology 51: 15–28.
  • 110
    Brias B, Bouchard JP, Xie YG, Rochefort DL, Chretien N, Tome FM, Lafreniere RG, Rommens JM, Uyama E, Nohira O, Blumen S, Korczyn AD, Heutink P, Mathieu J, Duranceau A, Codère F, Fardeau M, Rouleau GA ( 1998) Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nat Genet 18: 164–167.
  • 111
    Han Y, Jin BS, Lee SB, Sohn Y, Joung JW, Lee JH ( 2007) Effects of sugar additives on protein stability of recombinant human serum albumin during lyophilization and storage. Arch Pharm Res 30: 1124–1131.
  • 112
    Roy S, Henderson I, Nayar R, Randolph TW, Carpenter JF ( 2008) Effect of pH on stability of recombinant botulinum serotype A vaccine in aqueous solution and during storage of freeze-dried formulations. J Pharm Sci 97: 5132–5146.
    Direct Link:
  • 113
    Schüle S, Schulz-Fademrecht T, Garidel P, Bechtold-Peters K, Frieß W. Stabilization of IgG1 in spray-dried powders for inhalation. Eur J Pharm Biopharm 69: 793–807.
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