Volume 31, Issue 5 pp. 1122-1126

RESEARCH ARTICLE

Lyophilized hemoglobin-albumin cluster with disaccharides: Long-term storable powder of artificial O₂-carrier

Ryosuke Funaki,

Ryosuke Funaki

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Hitomi Iwasaki,

Hitomi Iwasaki

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Tomonori Kashima,

Tomonori Kashima

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Teruyuki Komatsu,

Corresponding Author

Teruyuki Komatsu

[email protected]

orcid.org/0000-0002-7622-3433

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

Correspondence

Prof Teruyuki Komatsu, Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.

Email: [email protected]

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Ryosuke Funaki,

Ryosuke Funaki

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Hitomi Iwasaki,

Hitomi Iwasaki

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Tomonori Kashima,

Tomonori Kashima

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

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Teruyuki Komatsu,

Corresponding Author

Teruyuki Komatsu

[email protected]

orcid.org/0000-0002-7622-3433

Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, Tokyo, Japan

Correspondence

Prof Teruyuki Komatsu, Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.

Email: [email protected]

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First published: 03 February 2020

https://doi.org/10.1002/pat.4846

Citations: 1

Funding information: Chuo University; Japan Society for the Promotion of Science, Grant/Award Number: 18K19007

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Abstract

Core-shell protein cluster comprising a hemoglobin (Hb) in the center and human serum albumins (HSA) at the exterior, Hb-HSA₃ cluster, is an artificial O₂-carrier designed for use as a red blood cell (RBC) substitute. Lyophilization of the Hb-HSA₃ cluster solution ([Hb unit] = 5 g/dL) with sucrose and trehalose yielded stable pink powder, which can be stored for 2 years at 4°C. Addition of pure water to the powder regenerated the homogeneous solution. The O₂-binding properties and oxyHb rate have been unaltered during the storage period. Infrared spectroscopic studies revealed that the hydrogen bond between protein and sugar stabilizes three-dimensional structure of the cluster.

REFERENCES

1Mensink MA, Frijlink HW, van der Voort Maarschalk K, Hinrichs WLJ. How sugars protect proteins in the solid state and during drying (review): mechanisms of stabilization in relation to stress conditions. Eur J Pharm Biopharm. 2017; 114: 288-295.
10.1016/j.ejpb.2017.01.024
CAS PubMed Web of Science® Google Scholar
2Carpenter JF, Crowe JH. An infrared spectroscopic study of interactions of carbohydrates with dried proteins. Biochemistry. 1989; 28: 3916-3922.
10.1021/bi00435a044
CAS PubMed Web of Science® Google Scholar
3Johnston DS, Castelli F. The influence of sugars on the properties of freeze-dried lysozyme and hemoglobin. Thermochim Acta. 1989; 144: 195-208.
10.1016/0040-6031(89)85100-7
CAS Web of Science® Google Scholar
4Yoshioka S, Miyazaki T, Aso Y, Kawanishi T. Significance of local mobility in aggregation of β-galactosidase lyophilized with trehalose, sucrose or stachyose. Pharm Res. 2007; 24: 1660-1667.
10.1007/s11095-007-9296-2
CAS PubMed Web of Science® Google Scholar
5Lewis LM, Johnson RE, Oldroyd ME, et al. Characterizing the freeze-drying behaviour of model protein formulations. AAPS PharmSciTech. 2010; 11: 1580-1590.
10.1208/s12249-010-9530-9
CAS PubMed Web of Science® Google Scholar
6Tomita D, Kimura T, Hosaka H, et al. Covalent core-shell architecture of hemoglobin and human serum albumin as an artificial O₂ carrier. Biomacromolecules. 2013; 14: 1816-1825.
10.1021/bm400204y
CAS PubMed Web of Science® Google Scholar
7Shinohara R, Yamada T, Schade B, et al. Structural insights into a hemoglobin-albumin cluster in aqueous medium. J Phys Chem Lett. 2017; 8: 819-824.
10.1021/acs.jpclett.6b02907
CAS PubMed Web of Science® Google Scholar
8Morita Y, Yamada T, Kureishi M, Kihira K, Komatsu T. Quaternary structure analysis of a hemoglobin core in hemoglobin-albumin cluster. J Phys Chem B. 2018; 122: 12031-12039.
10.1021/acs.jpcb.8b10077
CAS PubMed Web of Science® Google Scholar
9Funaki R, Kashima T, Okamoto W, et al. Hemoglobin-albumin clusters prepared using N-succinimidyl 3-maleimidopropionate as an appropriate crosslinker. ACS Omega. 2019; 4: 3228-3233.
10.1021/acsomega.8b03474
CAS Web of Science® Google Scholar
10Haruki R, Kimura T, Iwasaki H, et al. Safety evaluation of hemoglobin-albumin cluster “HemoAct” as a red blood cell substitute. Sci Rep. 2015; 5(12778): 1-9.
Google Scholar
11Iwasaki H, Yokomaku K, Kureishi M, et al. Hemoglobin-albumin cluster: physiological responses after exchange transfusion into rats and blood circulation persistence in dogs. Artif Cells Nanomed Biotechnol. 2018; 46: S621-S629.
10.1080/21691401.2018.1505740
PubMed Web of Science® Google Scholar
12Birukou I, Schweers RL, Olson JS. Distal histidine stabilizes bound O₂ and acts as a gate for ligand entry in both subunits of adult human hemoglobin. J Biol Chem. 2010; 285: 8840-8854.
10.1074/jbc.M109.053934
CAS PubMed Web of Science® Google Scholar
13Fedorov MV, Goodman JM, Nerukh D, Schumm S. Self-assembly of trehalose molecules on a lysozyme surface: the broken glass hypothesis. Phys Chem Chem Phys. 2011; 13: 2294-2299.
10.1039/C0CP01705A
CAS PubMed Web of Science® Google Scholar
14Prestrelski SJ, Tedeschi N, Arakawa T, Carpenter JF. Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers. Biophys J. 1933; 65: 661-671.
10.1016/S0006-3495(93)81120-2
Web of Science® Google Scholar
15Remmele RL Jr, Stushnoff C, Carpenter JF. Real-time in situ monitoring of lysozyme during lyophilization using infrared spectroscopy: dehydration stress in the presence of sucrose. Pharm Res. 1977; 14: 1548-1555.
10.1023/A:1012170116311
Google Scholar
16Rahmelow K, Hübner W, Ackermann T. Infrared absorbances of protein side chains. Anal Biochem. 1997; 257: 1-11.
10.1006/abio.1997.2502
Web of Science® Google Scholar
17Barth A. Infrared spectroscopy of proteins. Biochim Biophys Acta. 2007; 1767: 1073-1101.
10.1016/j.bbabio.2007.06.004
CAS PubMed Web of Science® Google Scholar
18Cleland JL, Lam X, Kendrick B, et al. A specific molar ratio of stabilizer to protein is required for storage stability of a lyophilized monoclonal antibody. J Pharm Sci. 2001; 90: 310-321.
10.1002/1520-6017(200103)90:3<310::AID-JPS6>3.0.CO;2-R
CAS PubMed Web of Science® Google Scholar
19Meister E, Gieseler H. Freeze-dry microscopy of protein/sugar mixtures: drying behaviour interpretation of collapse temperatures and a comparison to corresponding glass transition data. J Pharm Sci. 2009; 98: 3072-3087.
10.1002/jps.21586
CAS PubMed Web of Science® Google Scholar
20Jain NK, Roy I. Effects of trehalose on protein structure. Protein Sci. 2008; 18: 24-36.
Web of Science® Google Scholar
21Lerbert A, Bordat P, Affouard F, Hédoux A, Guinet Y, Descamps M. How do trehalose, maltose, and sucrose influence some structural and dynamical properties of lysozyme? Insight from molecular dynamics simulations. J Phys Chem B. 2007; 111: 9410-9420.
10.1021/jp071946z
PubMed Web of Science® Google Scholar
22Ohtake S, Schebor C, Pelecek SP, de Pablo JJ. Effect of pH, counter ion, and phosphate concentration on the glass transition temperature of freeze-dried sugar-phosphate mixtures. Pharm Res. 2004; 21: 1615-1621.
10.1023/B:PHAM.0000041456.19377.87
CAS PubMed Web of Science® Google Scholar

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Volume31, Issue5

May 2020

Pages 1122-1126

Lyophilized hemoglobin-albumin cluster with disaccharides: Long-term storable powder of artificial O₂-carrier

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Lyophilized hemoglobin-albumin cluster with disaccharides: Long-term storable powder of artificial O2-carrier

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Lyophilized hemoglobin-albumin cluster with disaccharides: Long-term storable powder of artificial O₂-carrier