Abstract
Commonly observed chemical modifications that occur in proteins during their in vitro purification, storage, and handling are discussed. Covalent modifications described include deamidation and isoaspartate formation, cleavage of peptide bonds at aspartic acid residues, cystine destruction and thioldisulfide interchange, oxidation of cysteine and methionine residues, and the glycation and carbamylation of amino groups.
Article PDF
Similar content being viewed by others
References
Stadtman, E. R. (1990)Biochemistry 29, 6323–6331.
Stadtman, E. R. (1992)Science 257, 1220–1224.
Stadtman, E. R. and Oliver, C. N. (1991) J. Biol. Chem.266, 2005–2008.
Feeney, R. E. (1980) inChemical Deterioration of Proteins (Whitaker, J. R. and Fujimaki, M., eds.), American Chemical Society, Washington, DC Symposium Series 123, pp. 1–47.
Klibanov, A. M. (1989)TIBS 14, 141–144.
Bucke, C. (1981) inEnzymes and Food Processing (Birch, G. G., Blakebrough, N., and Parker, K. J., eds.), Applied Science, London, pp. 51–72.
Ng, T. K. and Kenealy, W. R. (1986) inGeneral, Molecular and Applied Microbiology of Thermophiles (Brock, T. D., ed.), Wiley, New York, pp. 197–215.
Volkin, D. B. and Klibanov, A. M. (1989) inProtein Function: A Practical Approach (Creighton, T. E., ed.), IRL, Oxford, pp. 1–24.
Volkin, D. B. and Middaugh, C. R. (1992) inStability of Protein Pharmaceuticals Part A—Chemical and Physical Pathways of Protein Degradation (Ahern, T. J. and Manning, M. C., eds.), Plenum, New York, pp. 215–247.
Pearlman, R. and Nguyen, T. (1992)J. Pharm. Pharmacol. 44, 178–185.
Manning, M. C., Patel, K., and Borchardt, R. T. (1989)Pharm. Res. 6, 903–918.
Clarke, S., Stephenson, R. C., and Lowenson, J. D. (1992) inStability of Protein Pharmaceuticals Part A—Chemical and Physical Pathways of Protein Degradation (Ahern, T. J. and Manning, M. C., eds.), Plenum, New York, pp. 1–29.
Lui, D. T. Y. (1992)TIBTECH 10, 364–369.
Wright, T. H. (1991)Crit. Rev. Biochem. Mol. Biol. 26, 1–52.
Robinson, A. B. and Rudd, C. J. (1974) inCurrent Topics in Cellular Regulation (Horecker, B. L. and Stadtman, E. R., eds.), Academic, New York, pp. 247–295.
Aswad, D. W. and Johnson, B. A. (1987)TIBS 12, 155–158.
Wright, H. T. and Robinson, A. B. (1982) inFrom Cyclotrons to Cytochromes (Kaplan, N. O. and Robinson, A. B., eds.), Academic, New York, pp. 727–743.
Tyler-Cross, R. and Schirch, V. (1991)J. Biol. Chem. 266, 22,549–22,556.
Geiger, T. and Clarke, S. (1987)J. Biol. Chem. 262, 785–794.
Stephenson, R. C. and Clarke, S. (1989)J. Biol. Chem. 264, 6164–6170.
Yüksel, K. U. and Gracy, R. W. (1986)Arch. Biochem. Biophys. 248, 452–459.
Kossiakoff, A. A. (1988)Science 240, 191–194.
Clarke, S. (1987)Int. J. Peptide Protein Res. 30, 808–821.
Zale, S. E. and Klibanov, A. M. (1986)Biochemistry 25, 5432–5444.
Manjula, B. N., Seetharama, A., and Vithayathil, P. J. (1977)Biochem. J. 165, 337–345.
Wearne, S. J. and Creighton, T. E. (1989)Proteins: Struc. Func. Genetics 5, 8–12.
DiDonato, A., Ciardiello, M. A., Nigris, M. D., Piccoli, R., Mazzarella, L., and D’Alessio, G. (1993)J. Biol. Chem. 268, 4745–4751.
Johnson, B. A., Shirokawa, J. M., Hancock, W. S., Spellman, M. W., Basa, L. J., and Aswad, D. W. (1989)J. Biol. Chem. 264, 14,262–14,271.
Frenz, J., Wu, S. L., and Hancock, W. S. (1989)J. Chrom. 480, 379–391.
Teshima, G., Stults, J. T., Ling, V., and Canova-Davis, E. (1991)J. Biol. Chem. 266, 13,544–13,547.
Tuong, A., Maftough, M., Ponthus, C., Whitechurch, O., Roitsch, C., and Picard, C. (1992)Biochemistry 31, 8291–8299.
Bischoff, R., Lepage, P., Jaquinod, M., Cauet, G., Acker-Klein, M., Clesse, D., Laporte, M., Bayol, A., Van Dorsselaer, A., and Roitsch, C. (1993)Biochemistry 32, 725–734.
Partridge, S. M. and David, H. F. (1950)Nature 165, 62–63.
Schultz, J. (1967)Meth. Enzymol. 11, 255–263.
Inglis, A. S. (1983)Meth. Enzymol. 91, 324–332.
Marcus, F. (1985)Int. J. Peptide Protein Res. 25, 542–546.
Piszkiewicz, D., Landon, M., and Smith, E. L. (1970)Biochem. Biophys. Res. Commun. 40, 1173–1178.
Ahern, T. J. and Klibanov, A. M. (1988)Meth. Biochem. Anal. 33, 91–127.
Dominguez, J. M., Acebal, C., Jimenez, J., Mata, I., Macarron, R., and Castillon, M. P. (1992)Biochem. J. 287, 583–588.
Hensel, R., Jakob, I., Scheer, H., and Lottspeich, F. (1992)Biochem. Soc. Symp. 58, 127–133.
George-Nascimento, C., Lowenson, J., Borissenko, M., Calderón, M., Medina-Selby, A., Kuo, J., Clarke, S., and Randolph, A. (1990)Biochemistry 29, 9584–9591.
Szoka, P. R., Schreiber, A. B., Chan, H., and Murthy, J. (1986)DNA 5, 11–20.
Baneyx, F. and Georgiou, G. (1992) inStability of Protein Pharmaceuticals Part A—Chemical and Physical Pathways of Protein Degradation (Ahern, T. J., and Manning, M. C., eds.), Plenum, New York, pp. 69–108.
Enfors, S. O. (1992)TIBTECH 10, 310–315.
Braxton, S. and Wells, J. A. (1992)Biochemistry 31, 7796–7801.
Higgins, D. L., Lamb, M. C., Young, S. L., Powers, D. B., and Anderson, S. (1990)Thromb. Res. 57, 527–539.
Miekka, S. I. (1983)Biochim. Biophys. Acta 748, 374–380.
Kowit, J. D. and Maloney, J. (1982)Anal. Biochem. 123, 86–93.
Rittenhouse, J. and Marcus, F. (1984)Anal. Biochem. 138, 442–448.
Geisow, M. J. (1992)TIBTECH 10, 432–441.
Creighton, T. E. (1988)Bio Essays 8, 57–63.
Creighton, T. E. (1989) inProtein Sructure: A Practical Approach (Creighton, T. E., ed.), IRL, Oxford, pp. 155–167.
Kosen, P. A. (1992) inStability of Protein Pharmaceuticals Part A—Chemical and Physical Pathways of Protein Degradation (Ahern, T. J. and Manning, M. C., eds.), Plenum, New York, pp. 31–67.
Whitaker, J. R. and Feeney, R. E. (1983)CRC Crit. Rev. Food Sci. Nutr. 19, 173–212.
Feeney, R. E. (1980) inChemical Deterioration of Proteins (Whitaker, J. R. and Fujimaki, M., eds.), American Chemical Society, Washington, DC, pp. 1–47.
Florence, T. M. (1980)Biochem. J. 189, 507–520.
Chang, J. Y. (1991)J. Biol. Chem. 266, 10,839–10,843.
Volkin, D. B. and Klibanov, A. M. (1987)J. Biol. Chem. 262, 2945–2950.
Brems, D. N., Brown, P. L., Bryant, C., Chance, R. E., Green, L. K., Long, H. B., Miller, A. A., Millican, R., Shields, J. E., and Frank, B. H. (1992)Protein Eng. 5, 519–525.
Ryle, A. P. and Sanger, F. (1955)Biochem. J. 60, 535–540.
Torchinsky, Y. M. (1981)Sulfur in Proteins, Pergamon, Oxford.
Gilbert, H. F. (1984)Meth. Enzymol. 107, 330–351.
Nishihara, T., Maeda, H., Okamoto, I., Oshida, T., Mizoguchi, T., and Terada, T. (1991)Biochem. Biophys. Res. Commun. 174, 580–585.
Tyagi, S. C. and Simon, S. R. (1992)Biochemistry 31, 10,584–10,590.
Liang, J. N. and Pelletier, M. R. (1988)Exp. Eye Res. 47, 17–25.
Fominaya, J. M. and Hofsteenge, J. (1992)J. Biol. Chem. 267, 24,655–24,660.
Liu, W. R., Langer, R., and Klibanov, A. M. (1991)Biotechnol. Bioeng. 37, 177–184.
Schmid, G., Lüdemann, H. D., and Jaenicke, R. (1978)Eur. J. Biochem. 86, 219–224.
Murase, N. and Franks, F. (1989)Biophys. Chem. 34, 293–300.
Linemeyer, D. L., Menke, J. G., Kelly, L. J., Disalvo, J., Soderman, D., Schaeffer, M. T., Ortega, S., Gimenez-Gallego, G., and Thomas, K. A. (1990)Growth Factors 3, 287–298.
Englea, K. A. and Maciag, T. (1992)J. Biol. Chem. 267, 11,307–11,315.
Ortega, S., Schaeffer, M. T., Soderman, D., Disalvo, J., Linemeyer, D. L., Gimenez-Gallego, G., and Thomas, K. A. (1991)J. Biol. Chem. 266, 5842–5846.
Volkin, D. B., Tsai, P. K., Dabora, J. M., Gress, J. O., Burke, C. J., Linhardt, R. J., and Middaugh, C. R. (1993)Arch. Biochem. Biophys. 300, 30–41.
Tomazic, S. J. and Klibanov, A. M. (1988)J. Biol. Chem. 263, 3086–3091.
Perry, L. J. and Wetzel, R. (1984)Science 266, 555–557.
Perry, L. J. and Wetzel, R. (1986)Biochemistry 25, 733–739.
Perry, L. J. and Wetzel, R. (1987)Protein Eng. 1, 101–105.
Wetzel, R., Perry, L. J., Mulkerrin, M. G., and Randall, L. M. (1990) inProtein Design and Development of New Therapeutics and Vaccines (Hook, J. B. and Poste, G., eds.), Plenum, New York, pp. 79–115.
Swaim, M. W. and Pizzo, S. V. (1988)J. Leuk. Biol. 43, 365–379.
Brot, N. and Weissbach, H. (1983)Arch. Biochem. Biophys. 223, 271–281.
Brot, N., Fliss, H., Coleman, T., and Weissbach, H. (1984)Meth. Enzymol. 107, 352–360.
Hall, P. K. and Roberts, R. C. (1992)Biochim. Biophys. Acta 1121, 325–330.
Horowitz, P. M., Butler, M., and McClure, G. D. (1992)J. Biol. Chem. 267, 23,596–23,600.
Costa, M., Pecci, L., Pensa, B., and Cannella, C. (1977)Biochem. Biophys. Res. Commun. 78, 596–603.
Przysiecki, C. T., Joyce, J. G., Keller, P. M., Markus, H. Z., Carty, C. E., Hagopian, A., Sardana, M. K., Dunwiddie, C. T., Ellis, R. W., Miller, W. J., and Lehman, E. D. (1992)Protein Expr. Purif. 3, 185–195.
Pikal, M. J., Dellerman, K. M., Roy, M. L., and Riggin, R. M. (1991)Pharm. Res. 8, 427–436.
Stauffer, C. E. and Etson, D. (1969)J. Biol. Chem. 244, 5333–5338.
Estell, D. A., Graycar, T. P., and Wells, J. A. (1985)J. Biol. Chem. 260, 6518–6521.
Bott, R., Ultsch, M., Kossiakoff, A., Graycar, T., Katz, B., and Power, S. (1988)J. Biol. Chem. 263, 7895–7906.
Schwimmer, S. (1981)Source Book of Food Enzymology, Avi, Westport.
Yamamoto, O. (1992) inStability of Protein Pharmaceuticals Part A—Chemical and Physical Pathways of Protein Degradation (Ahern, T. J. and Manning, M. C., eds.), Plenum, New York, pp. 361–421.
Creed, D. (1984)Photochem. Photobiol. 39, 537–562.
Creed, D. (1984)Photochem. Photobiol. 39, 563–575.
Creed, D. (1984)Photochem. Photobiol. 39, 577–583.
Tassin, J. D. and Borkman, R. F. (1980)Photochem. Photobiol. 32, 577–585.
Pigault, C. and Gerard, D. (1984)Photochem. Photobiol. 40, 291–296.
Andley, U. P. and Clark, B. A. (1988)Curr. Eye Res. 7, 571–579.
Spodheim-Maurizot, M., Charlier, M., and Helene, C. (1985)Photochem. Photobiol. 42, 353–359.
Okajima, T., Kawata, Y., and Hamaguchi, K. (1990)Biochemistry 29, 9168–9175.
Timasheff, S. N. and Arakawa T. (1992) inProtein Structure: A Practical Approach (Creighton, T. E., ed.), IRL, Oxford, pp. 331–345.
Carpenter, J. F. and Crowe, J. H. (1988)Cryobiol. 25, 244–255.
Gottschalk, A. (1972) inGlycoproteins: Their Composition, Structure and Function (Gottschalk, A., ed.), Elsevier, Amsterdam, pp. 141–157.
Harding, J. J. (1991)Lens Eye Tox. Res. 8, 245–250.
Vlassara, H., Fuh, H., Makita, Z., Krungkrai, S., Cerami, A., and Bucala, R. (1992)Proc. Natl. Acad. Sci. USA 89, 12,043–12,047.
Bunn, H. F., Gabbay, K. H., and Gallop, P. M. (1978)Science 200, 21–27.
Elbe, A. S., Thorpe, S. R., and Baynes, J. W. (1983)J. Biol. Chem. 258, 9406–9412.
Suárez, G., Rajaram, R., Oronsky, A. L., and Gawinowicz, M. A. (1989)J. Biol. Chem. 264, 3674–3679.
Liang, J. N. and Rossi, M. T. (1990)Exp. Eye Res. 50, 367–371.
Stark, G. R., Stein, W. H., and Moore, S. (1960)J. Biol. Chem. 235, 3177–3181.
Stark, G. R. (1965)Biochemistry 4, 1030–1036.
Qin, W., Smith, J. B., and Smith, D. L. (1992)J. Biol. Chem. 267, 26,128–26,133.
Nowicki, C. and Santomé, J. A. (1981)Int. J. Peptide Protein Res. 18, 52–60.
Oimomi, M., Hatanaka, H., Yoshimura, Y., Yokono, K., Baba, S., and Taketomi, Y. (1987)Nephron 46, 63–66.
Lee, T. C. K. and Gibson, Q. H. (1981)J. Biol. Chem. 256, 4570–4577.
Steinbrecher, U. P., Fischer, M., Witztum, J. L., and Curtiss, L. K. (1984)J. Lipid Res. 25, 1109–1116.
Horiuchi, S., Araki, N., and Morino, Y. (1991)J. Biol. Chem. 266, 7329–7332.
Lehrman, S. R., Hamlin, D. M., Lund, M. E., and Walker, G. A. (1992)J. Protein Chem. 11, 657–663.
Wingfield, P. T., Mattaliano, R. J., MacDonald, H. R., Craig, S., Clore, G. M., Gronenborn, A. M., and Schmeissner, U. (1987)Protein Eng. 1, 413–417.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Volkin, D.B., Mach, H. & Middaugh, C.R. Degradative covalent reactions important to protein stability. Mol Biotechnol 8, 105–122 (1997). https://doi.org/10.1007/BF02752255
Issue Date:
DOI: https://doi.org/10.1007/BF02752255