Site-specific pegylation of therapeutic proteins

International Journal of Molecular Sciences

Volumn 16, Issue 10, 2015, Pages 25831-25864

  Dozier, Jonathan K ^a   Distefano, Mark D ^a,b  

^a University of Minnesota   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

Chemical modification; Enzymatic modification; PEGylation; Protein PEGylation; Site specific modification; Therapeutic proteins

Indexed keywords

APOMYOGLOBIN; CHYMOTRYPSIN A; COLONY STIMULATING FACTOR 1; CYSTEINE; FIBROBLAST GROWTH FACTOR 21; FORMYLGLYCINE GENERATING ENZYME; GRANULOCYTE COLONY STIMULATING FACTOR; HUMAN GROWTH HORMONE; INTERFERON BETA SERINE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 2; INTERLEUKIN 8; MACROGOL; MESSENGER RNA; PEPTIDES AND PROTEINS; POLYHISTIDINE TAG; PROTEIN FARNESYLTRANSFERASE; PROTEIN GLUTAMINE GAMMA GLUTAMYLTRANSFERASE; RECOMBINANT PROTEIN; SALCATONIN; SERINE; THERAPEUTIC PROTEIN; THREONINE; TRANSFER RNA; TYROSINE; UNCLASSIFIED DRUG; DRUG CARRIER; MACROGOL DERIVATIVE; PEPTIDE;

AMINO ACID SEQUENCE; AUXOTROPHY; CHEMICAL LABELING; ENZYME ACTIVITY; HUMAN; IMMUNE RESPONSE; NONHUMAN; NONSENSE MUTATION; PEPTIDE SYNTHESIS; PHAGOCYTOSIS; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PROCESSING; PROTEIN STRUCTURE; REVIEW; SITE SPECIFIC PEGYLATION; SYNTHESIS; TUMOR GROWTH; BIOCATALYSIS; CHEMISTRY; SOLID PHASE SYNTHESIS;

BIOCATALYSIS; DRUG CARRIERS; PEPTIDES; POLYETHYLENE GLYCOLS; SOLID-PHASE SYNTHESIS TECHNIQUES;

EID: 84968857097     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms161025831     Document Type: Review

References (126)

1. Leader, B.; Baca, Q. J.; Golan, D. E. Protein therapeutics: A summary and pharmacological classification. Nat. Rev. Drug Discov. 2008, 7, 21–39.
2. Carter, P. J. Introduction to current and future protein therapeutics: A protein engineering perspective. Exp. Cell Res. 2011, 317, 1261–1269.
3. Szymkowski, D. E. Creating the next generation of protein therapeutics through rational drug design. Curr. Opin. Drug Discov. Dev. 2005, 8, 590–600.
4. De Groot, A. S.; Scott, D. W. Immunogenicity of protein therapeutics. Trends Immunol. 2007, 28, 482–490.
5. Kromminga, A.; Schellekens, H. Antibodies against erythropoietin and other protein-based therapeutics: An overview. Ann. N. Y. Acad. Sci. 2005, 1050, 257–265.
6. Nagata, S.; Pastan, I. Removal of B cell epitopes as a practical approach for reducing the immunogenicity of foreign protein-based therapeutics. Adv. Drug Deliv. Rev. 2009, 61, 977–985.
7. Kontermann, R. E. Strategies for extended serum half-life of protein therapeutics. Curr. Opin. Biotechnol. 2011, 22, 868–876.
8. Szlachcic, A.; Zakrzewska, M.; Otlewski, J. Longer action means better drug: Tuning up protein therapeutics. Biotechnol. Adv. 2011, 29, 436–441.
9. Chen, C.; Constantinou, A.; Chester, K. A.; Vyas, B.; Canis, K.; Haslam, S. M.; Dell, A.; Epenetos, A. A.; Deonarain, M. P. Glycoengineering approach to half-life extension of recombinant biotherapeutics. Bioconjug. Chem. 2012, 23, 1524–1533.
10. Hutt, M.; Färber-Schwarz, A.; Unverdorben, F.; Richter, F.; Kontermann, R. E. Plasma half-life extension of small recombinant antibodies by fusion to immunoglobulin-binding domains. J. Biol. Chem. 2012, 287, 4462–4469.
11. Trüssel, S.; Dumelin, C.; Frey, K.; Villa, A.; Buller, F.; Neri, D. New strategy for the extension of the serum half-life of antibody fragments. Bioconjug. Chem. 2009, 20, 2286–2292.
12. Gaberc-Porekar, V.; Zore, I.; Podobnik, B.; Menart, V. Obstacles and pitfalls in the PEGylation of therapeutic proteins. Curr. Opin. Drug Discov. Dev. 2008, 11, 242–250.
13. Veronese, F. M.; Mero, A. The impact of PEGylation on biological therapies. BioDrugs 2008, 22, 315–329.
14. Abuchowski, A.; van Es, T.; Palczuk, N. C.; Davis, F. F. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J. Biol. Chem. 1977, 252, 3578–3581.
15. Abuchowski, A.; McCoy, J. R.; Palczuk, N. C.; van Es, T.; Davis, F. F. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J. Biol. Chem. 1977, 252, 3582–3586.
16. Chen, R. H. L.; Abuchowski, A.; van Es, T.; Palczuk, N. C.; Davis, F. F. Properties of two urate oxidases modified by the covalent attachment of poly (ethylene glycol). Biochim. Biophys. Acta Enzymol. 1981, 660, 293–298.
17. Savoca, K. V.; Abuchowski, A.; van Es, T.; Davis, F. F.; Palczuk, N. C. Preparation of a non-immunogenic arginase by the covalent attachment of polyethylene glycol. Biochim. Biophys. Acta Protein Struct. 1979, 578, 47–53.
18. Levy, Y.; Hershfield, M. S.; Fernandez-Mejia, C.; Polmar, S. H.; Scudiery, D.; Berger, M.; Sorensen, R. U. Adenosine deaminase deficiency with late onset of recurrent infections: Response to treatment with polyethylene glycol-modified adenosine deaminase. J. Pediatr. 1988, 113, 312–317.
19. Hershfield, M. S.; Buckley, R. H.; Greenberg, M. L.; Melton, A. L.; Schiff, R.; Hatem, C.; Kurtzberg, J.; Markert, M. L.; Kobayashi, R. H.; Kobayashi, A. L. Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N. Engl. J. Med. 1987, 316, 589–596.
20. McHutchison, J. G.; Lawitz, E. J.; Shiffman, M. L.; Muir, A. J.; Galler, G. W.; McCone, J.; Nyberg, L. M.; Lee, W. M.; Ghalib, R. H.; Schiff, E. R.; et al. Peginterferon α-2b or α-2a with ribavirin for treatment of hepatitis c infection. N. Engl. J. Med. 2009, 361, 580–593.
21. Lau, G. K. K.; Piratvisuth, T.; Luo, K. X.; Marcellin, P.; Thongsawat, S.; Cooksley, G.; Gane, E.; Fried, M. W.; Chow, W. C.; Paik, S. W.; et al. Peginterferon α-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis b. N. Engl. J. Med. 2005, 352, 2682–2695.
22. Wursthorn, K.; Lutgehetmann, M.; Dandri, M.; Volz, T.; Buggisch, P.; Zollner, B.; Longerich, T.; Schirmacher, P.; Metzler, F.; Zankel, M.; et al. Peginterferon α-2b plus adefovir induce strong cccDNA decline and HBsAg reduction in patients with chronic hepatitis b. Hepatology 2006, 44, 675–684.
23. Graham, M. L. Pegaspargase: A review of clinical studies. Adv. Drug Deliv. Rev. 2003, 55, 1293–1302.
24. Sherman, M. R.; Saifer, M. G. P.; Perez-Ruiz, F. Peg-uricase in the management of treatment-resistant gout and hyperuricemia. Adv. Drug Deliv. Rev. 2008, 60, 59–68.
25. Foser, S.; Schacher, A.; Weyer, K. A.; Brugger, D.; Dietel, E.; Marti, S.; Schreitmüller, T. Isolation, structural characterization, and antiviral activity of positional isomers of monoPEGylated interferon α-2a (pegasys). Protein Expr. Purif. 2003, 30, 78–87.
26. Wang, Y.-S.; Youngster, S.; Grace, M.; Bausch, J.; Bordens, R.; Wyss, D. F. Structural and biological characterization of PEGylated recombinant interferon α-2b and its therapeutic implications. Adv. Drug Deliv. Rev. 2002, 54, 547–570.
27. Finn, R. F. PEGylation of human growth hormone: Strategies and properties. In PEGylated Protein Drugs: Basic Science and Clinical Applications; Birkhauser Verlag: Birkhauser Verlag, Basel, Switzerland, 2009; pp. 187–203.
28. Fishburn, C. S. The pharmacology of PEGylation: Balancing PD with PK to generate novel therapeutics. J. Pharm. Sci. 2008, 97, 4167–4183.
29. Alconcel, S. N.; Baas, A. S.; Maynard, H. D. FDA-approved poly (ethylene glycol)-protein conjugate drugs. Polym. Chem. 2011, 2, 1442–1448.
30. Piedmonte, D. M.; Treuheit, M. J. Formulation of neulasta® (pegfilgrastim). Adv. Drug Deliv. Rev. 2008, 60, 50–58.
31. Pradhananga, S.; Wilkinson, I.; Ross, R. Pegvisomant: Structure and function. J. Mol. Endocrinol. 2002, 29, 11–14.
32. Macdougall, I. C.; Eckardt, K. Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia. Lancet 2006, 368, 947–953.
33. Blick, S. K. A.; Curran, M. P. Certolizumab pegol. BioDrugs 2007, 21, 195–201.
34. Schlesinger, N.; Yasothan, U.; Kirkpatrick, P. Pegloticase. Nat. Rev. Drug Discov. 2011, 10, 17–18.
35. Woodburn, K. W.; Fong, K.-L.; Wilson, S. D.; Sloneker, S.; Strzemienski, P.; Solon, E.; Moriya, Y.; Tagawa, Y. Peginesatide clearance, distribution, metabolism, and excretion in monkeys following intravenous administration. Drug Metab. Dispos. 2013, 41, 774–784.
36. Melmed, G. Y.; Targan, S. R.; Yasothan, U.; Hanicq, D.; Kirkpatrick, P. Certolizumab pegol. Nat. Rev. Drug Discov. 2008, 7, 641–642.
37. Ordas, I.; Mould, D. R.; Feagan, B. G.; Sandborn, W. J. Anti-TNF monoclonal antibodies in inflammatory bowel disease: Pharmacokinetics-based dosing paradigms. Clin. Pharmacol. Ther. 2012, 91, 635–646.
38. Goel, N.; Stephens, S. Certolizumab pegol. MAbs 2010, 2, 137–147.
39. Kinstler, O.; Brems, D.; Lauren, S.; Paige, A.; Hamburger, J.; Treuheit, M. Characterization and stability of N-terminally PEGylated rhG-CSF. Pharm. Res. 1996, 13, 996–1002.
40. Molineux, G. Pegfilgrastim: Using PEGylation technology to improve neutropenia support in cancer patients. Anticancer Drugs 2003, 14, 259–264.
41. Holmes, F. A.; O’Shaughnessy, J. A.; Vukelja, S.; Jones, S. E.; Shogan, J.; Savin, M.; Glaspy, J.; Moore, M.; Meza, L.; Wiznitzer, I.; et al. Blinded, randomized, multicenter study to evaluate single administration pegfilgrastim once per cycle versus daily filgrastim as an adjunct to chemotherapy in patients with high-risk stage II or stage III/IV breast cancer. J. Clin. Oncol. 2002, 20, 727–731.
42. Green, M. D.; Koelbl, H.; Baselga, J.; Galid, A.; Guillem, V.; Gascon, P.; Siena, S.; Lalisang, R. I.; Samonigg, H.; Clemens, M.R.; et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim vs. daily filgrastim in patients receiving myelosuppressive chemotherapy. Ann. Oncol. 2003, 14, 29–35.
43. Lindsley, C. W. The top prescription drugs of 2012 globally: Biologics dominate, but small molecule CNS drugs hold on to top spots. ACS Chem. Neurosci. 2013, 4, 905–907.
44. Pasut, G.; Veronese, F. M. State of the art in PEGylation: The great versatility achieved after forty years of research. J. Control. Release 2012, 161, 461–472.
45. Jevševar, S.; Kunstelj, M.; Porekar, V. G. PEGylation of therapeutic proteins. Biotechnol. J. 2010, 5, 113–128.
46. Kling, J. PEGylation of biologics: A multipurpose solution. BioProc. Int. 2013, 11, 3.
47. Roberts, M. J.; Bentley, M. D.; Harris, J. M. Chemistry for peptide and protein PEGylation. Adv. Drug Deliv. Rev. 2012, 64, 116–127.
48. Jølck, R. I.; Berg, R. H.; Andresen, T. L. Solid-phase synthesis of PEGylated lipopeptides using click chemistry. Bioconjug. Chem. 2010, 21, 807–810.
49. Pandey, B. K.; Smith, M. S.; Torgerson, C.; Lawrence, P. B.; Matthews, S. S.; Watkins, E.; Groves, M. L.; Prigozhin, M. B.; Price, J. L. Impact of site-specific PEGylation on the conformational stability and folding rate of the Pin WW domain depends strongly on PEG oligomer length. Bioconjug. Chem. 2013, 24, 796–802.
50. Price, J. L.; Powers, E. T.; Kelly, J. W. N-PEGylation of a reverse turn is stabilizing in multiple sequence contexts, unlike N-glcnacylation. ACS Chem. Biol. 2011, 6, 1188–1192.
51. Zalipsky, S.; Menon-Rudolph, S. In Hydrazide Derivatives of Poly (Ethylene Glycol) and Their Bioconjugates; ACS Publications: Washington, DC, USA, 1997; pp. 318–341.
52. Kinstler, O.; Molineux, G.; Treuheit, M.; Ladd, D.; Gegg, C. Mono-N-terminal poly (ethylene glycol)-protein conjugates. Adv. Drug Deliv. Rev. 2002, 54, 477–485.
53. Lee, H.; Jang, I.; Ryu, S.; Park, T. N-terminal site-specific mono-PEGylation of epidermal growth factor. Pharm. Res. 2003, 20, 818–825.
54. Unterweger, B.; Stoisser, T.; Leitgeb, S.; Birner-Grünberger, R.; Nidetzky, B. Engineering of aerococcus viridansl-lactate oxidase for site-specific PEGylation: Characterization and selective bioorthogonal modification of a S218C mutant. Bioconjug. Chem. 2012, 23, 1406–1414.
55. Gao, M.; Tong, Y.; Gao, X.; Yao, W. Development of a C-terminal site-specific PEGylated analog of GLP-1 with improved anti-diabetic effects in diabetic mice. Drug Dev. Res. 2013, 74, 186–193.
56. Qiu, H.; Boudanova, E.; Park, A.; Bird, J. J.; Honey, D. M.; Zarazinski, C.; Greene, B.; Kingsbury, J. S.; Boucher, S.; Pollock, J.; et al. Site-specific PEGylation of human thyroid stimulating hormone to prolong duration of action. Bioconjug. Chem. 2013, 24, 408–418.
57. Kim, T. H.; Jiang, H. H.; Lim, S. M.; Youn, Y. S.; Choi, K. Y.; Lee, S.; Chen, X.; Byun, Y.; Lee, K. C. Site-specific PEGylated exendin-4 modified with a high molecular weight trimeric PEG reduces steric hindrance and increases type 2 antidiabetic therapeutic effects. Bioconjug. Chem. 2012, 23, 2214–2220.
58. Xu, J.; Bussiere, J.; Yie, J.; Sickmier, A.; An, P.; Belouski, E.; Stanislaus, S.; Walker, K. W. Polyethylene glycol modified FGF21 engineered to maximize potency and minimize vacuole formation. Bioconjug. Chem. 2013, doi: 10.1021/bc300603k.
59. Danial, M.; van Dulmen, T. H. H.; Aleksandrowicz, J.; Pötgens, A. J. G.; Klok, H. Site-specific PEGylation of HR2 peptides: Effects of PEG conjugation position and chain length on HIV-1 membrane fusion inhibition and proteolytic degradation. Bioconjug. Chem. 2012, 23, 1648–1660.
60. Pan, L.; Wang, H.; Lai, J.; Xu, Y.; Zhang, C.; Chen, S. Site-specific PEGylation of a mutated-cysteine residue and its effect on tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). Biomaterials 2013, 34, 9115–9123.
61. Balan, S.; Choi, J.-W.; Godwin, A.; Teo, I.; Laborde, C. M.; Heidelberger, S.; Zloh, M.; Shaunak, S.; Brocchini, S. Site-specific PEGylation of protein disulfide bonds using a three-carbon bridge. Bioconjug. Chem. 2006, 18, 61–76.
62. Schumacher, F. F.; Nobles, M.; Ryan, C. P.; Smith, M. E. B.; Tinker, A.; Caddick, S.; Baker, J. R. In situ maleimide bridging of disulfides and a new approach to protein PEGylation. Bioconjug. Chem. 2011, 22, 132–136.
63. Robin, M. P.; Wilson, P.; Mabire, A. B.; Kiviaho, J. K.; Raymond, J. E.; Haddleton, D. M.; O’Reilly, R. K. Conjugation-induced fluorescent labeling of proteins and polymers using dithiomaleimides. J. Am. Chem. Soc. 2013, 135, 2875–2878.
64. Badescu, G.; Bryant, P.; Bird, M.; Henseleit, K.; Swierkosz, J.; Parekh, V.; Tommasi, R.; Pawlisz, E.; Jurlewicz, K.; Farys, M.; et al. Bridging disulfides for stable and defined antibody drug conjugates. Bioconjug. Chem. 2014, 25, 1124–1136.
65. Ban, H.; Gavrilyuk, J.; Barbas, C. F. Tyrosine bioconjugation through aqueous ene-type reactions: A click-like reaction for tyrosine. J. Am. Chem. Soc. 2010, 132, 1523–1525.
66. Ban, H.; Nagano, M.; Gavrilyuk, J.; Hakamata, W.; Inokuma, T.; Barbas, C. F. Facile and stabile linkages through tyrosine: Bioconjugation strategies with the tyrosine-click reaction. Bioconjug. Chem. 2013, 24, 520–532.
67. Gaertner, H. F.; Offord, R. E. Site-specific attachment of functionalized poly (ethylene glycol) to the amino terminus of proteins. Bioconjug. Chem. 1996, 7, 38–44.
68. Levine, P. M.; Craven, T. W.; Bonneau, R.; Kirshenbaum, K. Intrinsic bioconjugation for site-specific protein PEGylation at N-terminal serine. Chem. Commun. 2014, 50, 6909–6912.
69. Cheung, R. C. F.; Wong, J. H.; Ng, T. B. Immobilized metal ion affinity chromatography: A review on its applications. Appl. Microbiol. Biot. 2012, 96, 1411–1420.
70. Terpe, K. Overview of tag protein fusions: From molecular and biochemical fundamentals to commercial systems. Appl. Microbiol. Biot. 2003, 60, 523–533.
71. Kim, T. H.; Swierczewska, M.; Oh, Y.; Kim, A.; Jo, D. G.; Park, J. H.; Byun, Y.; Sadegh-Nasseri, S.; Pomper, M. G.; Lee, K.C.; et al. Mix to validate: A facile, reversible PEGylation for fast screening of potential therapeutic proteins in vivo. Angew. Chem. Int. Ed. 2013, 52, 6880–6884.
72. Cong, Y.; Pawlisz, E.; Bryant, P.; Balan, S.; Laurine, E.; Tommasi, R.; Singh, R.; Dubey, S.; Peciak, K.; Bird, M.; et al. Site-specific PEGylation at histidine tags. Bioconjug. Chem. 2012, 23, 248–263.
73. Thom, J.; Anderson, D.; McGregor, J.; Cotton, G. Recombinant protein hydrazides: Application to site-specific protein PEGylation. Bioconjug. Chem. 2011, 22, 1017–1020.
74. Sletten, E. M.; Bertozzi, C. R. Bioorthogonal chemistry: Fishing for selectivity in a sea of functionality. Angew. Chem. Int. Ed. 2009, 48, 6974–6998.
75. De Graaf, A. J.; Kooijman, M.; Hennink, W. E.; Mastrobattista, E. Nonnatural amino acids for site-specific protein conjugation. Bioconjug. Chem. 2009, 20, 1281–1295.
76. Cazalis, C. S.; Haller, C. A.; Sease-Cargo, L.; Chaikof, E. L. C-Terminal site-specific PEGylation of a truncated thrombomodulin mutant with retention of full bioactivity. Bioconjug. Chem. 2004, 15, 1005–1009.
77. Nairn, N. W.; Shanebeck, K. D.; Wang, A.; Graddis, T. J.; VanBrunt, M. P.; Thornton, K. C.; Grabstein, K. Development of copper-catalyzed azide-alkyne cycloaddition for increased in vivo efficacy of interferon β-1b by site-specific PEGylation. Bioconjug. Chem. 2012, 23, 2087–2097.
78. Wang, L.; Xie, J.; Schultz, P. G. Expanding the genetic code. Annu. Rev. Biophys. Biomol. Struct. 2006, 35, 225–249.
79. Kim, C. H.; Axup, J. Y.; Schultz, P. G. Protein conjugation with genetically encoded unnatural amino acids. Curr. Opin. Chem. Biol. 2013, 17, 412–419.
80. Chin, J. W.; Santoro, S. W.; Martin, A. B.; King, D. S.; Wang, L.; Schultz, P. G. Addition of p-azido-L-phenylalanine to the genetic code of Escherichia coli. J. Am. Chem. Soc. 2002, 124, 9026–9027.
81. Deiters, A.; Cropp, T. A.; Summerer, D.; Mukherji, M.; Schultz, P. G. Site-specific PEGylation of proteins containing unnatural amino acids. Bioorg. Med. Chem. Lett. 2004, 14, 5743–5745.
82. Dumas, A.; Spicer, C. D.; Gao, Z.; Takehana, T.; Lin, Y. A.; Yasukohchi, T.; Davis, B. G. Self-liganded Suzuki–Miyaura coupling for site-selective protein PEGylation. Angew. Chem. Int. Ed. 2013, 52, 3916–3921.
83. Li, Y.; Yang, M.; Huang, Y.; Song, X.; Liu, L.; Chen, P. R. Genetically encoded alkenyl-pyrrolysine analogues for thiol-ene reaction mediated site-specific protein labeling. Chem. Sci. 2012, 3, 2766–2770.
84. Cho, H.; Daniel, T.; Buechler, Y. J.; Litzinger, D. C.; Maio, Z.; Putnam, A.-M. H.; Kraynov, V. S.; Sim, B.-C.; Bussell, S.; Javahishvili, T. Optimized clinical performance of growth hormone with an expanded genetic code. Proc. Natl. Acad. Sci. USA 2011, 108, 9060–9065.
85. Mu, J.; Pinkstaff, J.; Li, Z.; Skidmore, L.; Li, N.; Myler, H.; Dallas-Yang, Q.; Putnam, A.-M.; Yao, J.; Bussell, S.; et al. FGF21 analogs of sustained action enabled by orthogonal biosynthesis demonstrate enhanced antidiabetic pharmacology in rodents. Diabetes 2012, 61, 505–512.
86. Rashidian, M.; Dozier, J. K.; Distefano, M. D. Enzymatic labeling of proteins: Techniques and approaches. Bioconjug. Chem. 2013, 24, 1277–1294.
87. Tsukiji, S.; Nagamune, T. Sortase-mediated ligation: A gift from gram-positive bacteria to protein engineering. ChemBioChem 2009, 10, 787–798.
88. Popp, M. W.; Antos, J. M.; Grotenbreg, G. M.; Spooner, E.; Ploegh, H. L. Sortagging: A versatile method for protein labeling. Nat. Chem. Biol. 2007, 3, 707–708.
89. Parthasarathy, R.; Subramanian, S.; Boder, E. T. Sortase A as a novel molecular “stapler” for sequence-specific protein conjugation. Bioconjug. Chem. 2007, 18, 469–476.
90. Popp, M. W.; Dougan, S. K.; Chuang, T.-Y.; Spooner, E.; Ploegh, H. L. Sortase-catalyzed transformations that improve the properties of cytokines. Proc. Natl. Acad. Sci. USA 2011, 108, 3169–3174.
91. Leung, M. K. M.; Hagemeyer, C. E.; Johnston, A. P. R.; Gonzales, C.; Kamphuis, M. M. J.; Ardipradja, K.; Such, G. K.; Peter, K.; Caruso, F. Bio-click chemistry: Enzymatic functionalization of PEGylated capsules for targeting applications. Angew. Chem. Int. Ed. 2012, 124, 7244–7248.
92. Tomita, U.; Yamaguchi, S.; Maeda, Y.; Chujo, K.; Minamihata, K.; Nagamune, T. Protein cell-surface display through in situ enzymatic modification of proteins with a poly (ethylene glycol)-lipid. Biotechnol. Bioeng. 2013, 110, 2785–2789.
93. Li, Y.-M.; Li, Y.-T.; Pan, M.; Kong, X.-Q.; Huang, Y.-C.; Hong, Z.-Y.; Liu, L. Irreversible site-specific hydrazinolysis of proteins by use of sortase. Angew. Chem. 2014, 126, 2230–2234.
94. Wang, Y.-C.; Distefano, M. D. Solid-phase synthesis of C-terminal peptide libraries for studying the specificity of enzymatic protein prenylation. Chem. Commun. 2012, 48, 8228–8230.
95. Duckworth, B. P.; Xu, J.; Taton, T. A.; Guo, A.; Distefano, M. D. Site-specific, covalent attachment of proteins to a solid surface. Bioconjug. Chem. 2006, 17, 967–974.
96. Duckworth, B. P.; Zhang, Z.; Hosokawa, A.; Distefano, M. D. Selective labeling of proteins by using protein farnesyltransferase. ChemBioChem 2007, 8, 98–105.
97. Rashidian, M.; Dozier, J. K.; Lenevich, S.; Distefano, M. D. Selective labeling of polypeptides using protein farnesyltransferase via rapid oxime ligation. Chem. Commun. 2010, 46, 8998–9000.
98. Rashidian, M.; Mahmoodi, M. M.; Shah, R.; Dozier, J. K.; Wagner, C. R.; Distefano, M. D. A highly efficient catalyst for oxime ligation and hydrazone-oxime exchange suitable for bioconjugation. Bioconjug. Chem. 2013, 24, 333–342.
99. Dursina, B.; Reents, R.; Delon, C.; Wu, Y.; Kulharia, M.; Thutewohl, M.; Veligodsky, A.; Kalinin, A.; Evstifeev, V.; Ciobanu, D.; et al. Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids. J. Am. Chem. Soc. 2006, 128, 2822–2835.
100. Maalouf, M. A.; Wiemer, A. J.; Kuder, C. H.; Hohl, R. J.; Wiemer, D. F. Synthesis of fluorescently tagged isoprenoid bisphosphonates that inhibit protein geranylgeranylation. Bioorgan. Med. Chem. 2007, 15, 1959–1966.
101. Turek, T. C.; Gaon, I.; Distefano, M. D.; Strickland, C. L. Synthesis of farnesyl diphosphate analogues containing ether-linked photoactive benzophenones and their application in studies of protein prenyltransferases. J. Org. Chem. 2001, 66, 3253–3264.
102. Völkert, M.; Uwai, K.; Tebbe, A.; Popkirova, B.; Wagner, M.; Kuhlmann, J.; Waldmann, H. Synthesis and biological activity of photoactivatable N-Ras peptides and proteins. J. Am. Chem. Soc. 2003, 125, 12749–12758.
103. Hovlid, M. L.; Edelstein, R. L.; Henry, O.; Ochocki, J.; DeGraw, A.; Lenevich, S.; Talbot, T.; Young, V. G.; Hruza, A. W.; Lopez-Gallego, F.; et al. Synthesis, properties, and applications of diazotrifluropropanoyl-containing photoactive analogs of farnesyl diphosphate containing modified linkages for enhanced stability. Chem. Biol. Drug Des. 2010, 75, 51–67.
104. Rashidian, M.; Song, J. M.; Pricer, R. E.; Distefano, M. D. Chemoenzymatic reversible immobilization and labeling of proteins without prior purification. J. Am. Chem. Soc. 2012, 134, 8455–8467.
105. Li, Q.; Hapka, D.; Chen, H.; Vallera, D. A.; Wagner, C. R. Self-assembly of antibodies by chemical induction. Angew. Chem. Int. Ed. 2008, 47, 10179–10182.
106. Volpato, J. P.; Mayotte, N.; Fossati, E.; Guerrero, V.; Sauvageau, G.; Pelletier, J. N. Selectively weakened binding of methotrexate by human dihydrofolate reductase allows rapid ex vivo selection of mammalian cells. J. Mol. Recognit. 2011, 24, 188–198.
107. Dozier, J. K.; Khatwani, S. L.; Wollack, J. W.; Wang, Y.-C.; Schmidt-Dannert, C.; Distefano, M. D. Engineering protein farnesyltransferase for enzymatic protein labeling applications. Bioconjug. Chem. 2014, 25, 1203–1212.
108. DeFrees, S.; Wang, Z.-G.; Xing, R.; Scott, A. E.; Wang, J.; Zopf, D.; Gouty, D. L.; Sjoberg, E. R.; Panneerselvam, K.; Brinkman-van der Linden, E. C. M.; et al. GlycoPEGylation of recombinant therapeutic proteins produced in Escherichia coli. Glycobiology 2006, 16, 833–843.
109. Stennicke, H. R.; Østergaard, H.; Bayer, R. J.; Kalo, M. S.; Kinealy, K.; Holm, P. K.; Sørensen, B. B.; Zopf, D.; Bjørn, S. E. Generation and biochemical characterization of glycoPEGylated factor VIIa derivatives. Thromb. Haemost. 2008, 100, 920–928.
110. Plesner, B.; Westh, P.; Nielsen, A. D. Biophysical characterisation of glycoPEGylated recombinant human factor VIIa. Int. J. Pharm. 2011, 406, 62–68.
111. Østergaard, H.; Bjelke, J. R.; Hansen, L.; Petersen, L. C.; Pedersen, A. A.; Elm, T.; Møller, F.; Hermit, M. B.; Holm, P. K.; Krogh, T.N.; et al. Prolonged half-life and preserved enzymatic properties of factor ix selectively PEGylated on native N-glycans in the activation peptide. Blood 2011, 118, 2333–2341.
112. Collins, P. W.; Moss, J.; Knobe, K.; Groth, A.; Colberg, T.; Watson, E. Population pharmacokinetic modeling for dose setting of nonacog beta pegol (N9-GP), a glycoPEGylated recombinant factor IX. J. Thromb. Haemost. 2012, 10, 2305–2312.
113. Stennicke, H. R.; Kjalke, M.; Karpf, D. M.; Balling, K. W.; Johansen, P. B.; Elm, T.; Øvlisen, K.; Möller, F.; Holmberg, H. L.; Gudme, C. N.; et al. A novel B-domain O-glycoPEGylated FVIII (N8-GP) demonstrates full efficacy and prolonged effect in hemophilic mice models. Blood 2013, 121, 2108–2116.
114. Park, A.; Honey, D. M.; Hou, L.; Bird, J. J.; Zarazinski, C.; Searles, M.; Braithwaite, C.; Kingsbury, J. S.; Kyazike, J.; Culm-Merdek, K.; et al. Carbohydrate-mediated polyethylene glycol conjugation of TSH improves its pharmacological properties. Endocrinology 2013, 154, 1373–1383.
115. Mero, A.; Schiavon, M.; Veronese, F. M.; Pasut, G. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone. J. Control. Release 2011, 154, 27–34.
116. Sato, H.; Ikeda, M.; Suzuki, K.; Hirayama, K. Site-specific modification of interleukin-2 by the combined use of genetic engineering techniques and transglutaminase. Biochemistry 1996, 35, 13072–13080.
117. Sato, H.; Hayashi, E.; Yamada, N.; Yatagai, M.; Takahara, Y. Further studies on the site-specific protein modification by microbial transglutaminase. Bioconjug. Chem. 2001, 12, 701–710.
118. Mero, A.; Spolaore, B.; Veronese, F. M.; Fontana, A. Transglutaminase-mediated PEGylation of proteins: Direct identification of the sites of protein modification by mass spectrometry using a novel monodisperse PEG. Bioconjug. Chem. 2009, 20, 384–389.
119. Fontana, A.; Spolaore, B.; Mero, A.; Veronese, F. M. Site-specific modification and PEGylation of pharmaceutical proteins mediated by transglutaminase. Adv. Drug Deliv. Rev. 2008, 60, 13–28.
120. Mariniello, L.; Porta, R.; Sorrentino, A.; Giosafatto, C. V. L.; Rossi Marquez, G.; Esposito, M.; di Pierro, P. Transglutaminase-mediated macromolecular assembly: Production of conjugates for food and pharmaceutical applications. Amino Acids 2014, 46, 767–776.
121. Rachel, N.; Pelletier, J. Biotechnological applications of transglutaminases. Biomolecules 2013, 3, 870–888.
122. Da Silva Freitas, D.; Mero, A.; Pasut, G. Chemical and enzymatic site specific PEGylation of hgh. Bioconjug. Chem. 2013, 24, 456–463.
123. Maullu, C.; Raimondo, D.; Caboi, F.; Giorgetti, A.; Sergi, M.; Valentini, M.; Tonon, G.; Tramontano, A. Site-directed enzymatic PEGylation of the human granulocyte colony-stimulating factor. FEBS J. 2009, 276, 6741–6750.
124. Zhao, X.; Shaw, A. C.; Wang, J.; Chang, C.; Deng, J.; Su, J. A novel high-throughput screening method for microbial transglutaminases with high specificity toward Gln141 of human growth hormone. J. Biomol. Screen. 2010, 15, 206–212.
125. Dierks, T.; Schmidt, B.; Borissenko, L. V.; Peng, J.; Preusser, A.; Mariappan, M.; von Figura, K. Multiple sulfatase deficiency is caused by mutations in the gene encoding the human cα-formylglycine generating enzyme. Cell 2003, 113, 435–444.
126. Carrico, I. S.; Carlson, B. L.; Bertozzi, C. R. Introducing genetically encoded aldehydes into proteins. Nat. Chem. Biol. 2007, 3, 321–322.