Sites of modification of hemospan, a poly(ethylene glycol)-modified human hemoglobin for use as an oxygen therapeutic

Bioconjugate Chemistry

Volumn 19, Issue 11, 2008, Pages 2163-2170

  Vandegriff, Kim D ^a   Malavalli, Ashok ^a   Mkrtchyan, Gnel M ^a   Spann, Stephanie N ^a   Baker, Dale A ^a,b   Winslow, Robert M ^a,b  

^a SANGART INC   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHAINS; ETHYLENE; OXYGEN; POLYETHYLENE GLYCOLS;

2-IMINOTHIOLANE; CLINICAL TRIAL; GLOBIN CHAINS; HAEMOGLOBINS; MALEIMIDES; POLY(ETHYLENE GLYCOL)(PEG); SITE-SPECIFIC; SPECIFIC CONJUGATIONS; THIOLATION; Β-GLOBIN;

HEMOGLOBIN;

2 IMINOTHIOLANE; ALPHA GLOBIN; BETA GLOBIN; HEMOGLOBIN; HEMOGLOBIN DERIVATIVE; HEMOSPAN; MACROGOL; MALEIMIDE; N ETHYLMALEIMIDE; OXYGEN; OXYHEMOGLOBIN; TETRAMER; UNCLASSIFIED DRUG;

ARTICLE; BINDING SITE; CHEMICAL REACTION; CONJUGATION; CONTROLLED STUDY; DRUG STRUCTURE; MALEIMIDATION; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; OXYGEN THERAPY; POLYACRYLAMIDE GEL ELECTROPHORESIS; PROTEIN ANALYSIS; PROTEIN MODIFICATION; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY;

EID: 56749179069     PISSN: 10431802     EISSN: None     Source Type: Journal    
DOI: 10.1021/bc8002666     Document Type: Article

References (21)

1. Acharya, A. S., Manjula, B. N., and Smith, P. (1996) Hemoglobin crosslinkers. U.S. Patent 5,585,484.
2. Vandegriff, K. D., Malavalli, A., Wooldridge, J., Lohman, J., and Winslow, R. M. (2003) MP4, a new nonvasoactive PEG-Hb conjugate. Transfusion 43, 509-516.
3. Manjula, B. N., Tsai, A., Upadhya, R., Perumalsamy, K., Smith, P. K., Malavalli, A., Vandegriff, K. D., Winslow, R. M., Intaglietta, M., Prabhakaran, M., Friedman, J. M., and Acharya, A. S. (2003) Site-specific PEGylation of hemoglobin at Cys-93(β): correlation between the colligative properties of the PEGylated protein and the length of the conjugated chain. Bioconjugate Chem. 14, 464-472.
4. 2 binding to a maleimide poly(ethylene glycol)-conjugated human haemoglobin. Biochem. J. 382, 183-189.
5. Vandegriff, K. D., Malavalli, A., Minn, C., Jiang, E., Lohman, J., Young, M. A., Samaja, M., and Winslow, R. M. (2006) Oxidation and haeme loss kinetics of poly(ethylene glycol)-conjugated hemoglobin (MP4): dissociation between in vitro and in vivo oxidation rates. Biochem. J. 399, 463-471.
6. Svergun, D. I., Ekström, F., Vandegriff, K. D., Malavalli, A., Baker, D. A., Nilsson, C., and Winslow, R. M. (2008) Solution structure of poly(ethylene) glycol-conjugated hemoglobin revealed by small-angle X-ray scattering: implications for a new oxygen therapeutic. Biophys. J. 94, 173-181.
7. Winslow, R. M., Lohman, J., Malavalli, A., and Vandegriff, K. D. (2004) Comparison of PEG-modified albumin and hemoglobin in extreme hemodilution in the rat. J. Appl. Physiol. 97, 1527-1534.
8. 2 therapeutics. Am. J. Physiol. 285, H1411-H1419.
9. Drobin, D., Kjellström, B. T., Malm, E., Malavalli, A., Lohman, J., Vandegriff, K. D., Young, M. A., and Winslow, R. M. (2004) Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4). J. Appl. Physiol. 96, 1843-1853.
10. Young, M. A., Riddez, L., Kjellström, B. T., Bursell, J., Winslow, F., Lohman, J., and Winslow, R. M. (2005) MalPEG-hemoglobin (MP4) improves hemodynamics, acid-base status, and survival after uncontrolled hemorrhage in anesthetized swine. Crit. Care Med. 33, 1794-1804.
11. Björkholm, M., Fagrell, B., Przybelski, R., Winslow, N., Young, M., and Winslow, R. M. (2005) A phase I single blind clinical trial of a new oxygen transport agent (MP4), human hemoglobin modified with maleimide-activated polyethylene glycol. Haematologica 90, 505-515.
12. Olofsson, C., Ahl, T., Johansson, T., Larsson, S., Nellgård, P., Ponzer, S., Fagrell, B., Przybelski, R., Keipert, P., Winslow, N., and Winslow, R. M. (2006) A multi-center clinical study of the safety and activity of maleimide-polyethylene glycol hemoglobin (Hemospan®) in patients undergoing major orthopedic surgery. Anesthesiology 105, 1153-1163.
13. Vandegriff, K. D., Young, M. A., Lohman, J., Bellelli, A., Samaja, M., Malavalli, A., and Winslow, R. M. (2008) CO-MP4, a poly(ethylene) glycol-conjugated hemoglobin derivative and carbon monoxide carrier that reduces myocardial infarct size in rats. Br. J. Pharmacol. 154, 1649-1661.
14. Iafelice, R., Cristoni, S., Caccia, D., Russo, R., Rossi-Bernardi, L., Lowe, K. C., and Perrella, M. (2007) Identification of the sites of deoxy haemoglobin pegylation. Biochem. J. 403, 189-196.
15. Ampulski, R., Ayers, V., and Morell, S. (1969) Determination of the reactive sulfhydryl groups in heme proteins with 4,4′-dipyridinedisulfide. Anal. Biochem. 32, 163-169.
16. Jackson, C. C., Charlton, J., Kuzminski, K., Lang, G., and Sehon, A. (1987) Synthesis, isolation, and characterization of conjugates of ovalbumin with monomethoxypolyethylene glycol using cyanuric chloride as the coupling agent. Anal. Biochem. 165, 114-127.
17. Kurfürst, M. M. (1992) Detection and molecular weight determination of polyethylene glycol-modified hirudin by staining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Anal. Biochem. 200, 244-248.
18. Skoog, B. (1979) Determination of polyethylene glycols 4000 and 6000 in plasma protein preparations. Vox Sang. 37, 345-349.
19. Masala, B., and Manca, L. (1994) Detection of globin chains by reversed-phase high-performance liquid chromatography. Methods Enzymol. 231, 21-44.
20. Park, S. Y., Yokoyama, T., Shibayama, N., Shiro, Y., and Tame, J. R. (2006) 1.25 Å resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms. J. Mol. Biol. 360, 690-701.
21. Porollo, A. A., Adamczak, R., and Meller, J. (2004) POLYVIEW: a flexible visualization tool for structural and functional annotations of proteins. Bioinformatics 20, 2460-2462.