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Methylglyoxal Induced Modifications to Stabilize Therapeutic Proteins: A Review

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Abstract

Therapeutic proteins are potent, fast-acting drugs that are highly effective in treating various conditions. Medicinal protein usage has increased in the past 10 years, and it will evolve further as we better understand disease molecular pathways. However, it is associated with high processing costs, limited stability, difficulty in being administered as an oral medication, and the inability of large proteins to penetrate tissue and reach their target locations. Many methods have been developed to overcome the problems with the stability and chaperone activity of therapeutic proteins, viz., the addition of external agents (changing the properties of the surrounding solvent by using stabilizing excipients, e.g., amino acids, sugars, polyols) and internal agents (chemical modifications that influence its structural properties, e.g., mutations, glycosylation). However, these methods must completely clear protein instability and chaperone issues. There is still much work to be done on finetuning chaperone proteins to increase their biological efficacy and stability. Methylglyoxal (MGO), a potent dicarbonyl compound, reacts with proteins and forms covalent cross-links. Much research on MGO scavengers has been conducted since they are known to alter protein structure, which may result in alterations in biological activity and stability. MGO is naturally produced within our body, however, its impact on chaperones and protein stability needs to be better understood and seems to vary based on concentration. This review highlights the efforts of several research groups on the effect of MGO on various proteins. It also addresses the impact of MGO on a client protein, α-crystallin, to understand the potential solutions to the protein’s chaperone and stability problems.

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References

  1. Global peptide therapeutics market & clinical trials insight 2028(2022). https://www.researchandmarkets.com/reports/5576687/global-peptide-therapeutics-market-and-clinical. Accessed 7 Aug 2023

  2. Bruno BJ, Miller GD, Lim CS (2013) Basics and recent advances in peptide and protein drug delivery. Ther Deliv 4:1443. https://doi.org/10.4155/TDE.13.104

    Article  CAS  PubMed  Google Scholar 

  3. Wang L, Wang N, Zhang W et al (2022) Therapeutic peptides: current applications and future directions. Signal Transduct Target Ther. https://doi.org/10.1038/S41392-022-00904-4

    Article  PubMed  PubMed Central  Google Scholar 

  4. Badal McCreath S, Delgoda R (2016) Pharmacognosy : fundamentals, applications and strategies. Academic press, Cambridge

    Google Scholar 

  5. Deller MC, Kong L, Rupp B (2016) Protein stability: a crystallographer’s perspective. Acta Crystallogr F Struct Biol Commun 72:72–95. https://doi.org/10.1107/S2053230X15024619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Manning MC, Chou DK, Murphy BM et al (2010) Stability of protein pharmaceuticals: an update. Pharm Res 27:544–575. https://doi.org/10.1007/S11095-009-0045-6

    Article  PubMed  Google Scholar 

  7. Sola RJ, Griebenow K (2009) Effects of glycosylation on the stability of protein pharmaceuticals. J Pharm Sci 98:1223–1245. https://doi.org/10.1002/JPS.21504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ramasamy R, Yan SF, Schmidt AM (2006) Methylglyoxal comes of age. Cell 124:258–260. https://doi.org/10.1016/J.CELL.2006.01.002

    Article  CAS  PubMed  Google Scholar 

  9. Lederer MO, Klaiber RG (1999) Cross-linking of proteins by maillard processes: characterization and detection of lysine-arginine cross-links derived from glyoxal and methylglyoxal. Bioorg Med Chem 7:2499–2507. https://doi.org/10.1016/S0968-0896(99)00212-6

    Article  CAS  PubMed  Google Scholar 

  10. Iannuzzi C, Irace G, Sirangelo I (2014) Differential effects of glycation on protein aggregation and amyloid formation. Front Mol Biosci 1:9–9. https://doi.org/10.3389/FMOLB.2014.00009

    Article  PubMed  PubMed Central  Google Scholar 

  11. Nagaraj RH, Oya-Ito T, Padayatti PS et al (2003) Enhancement of chaperone function of alpha-crystallin by methylglyoxal modification. Biochemistry 42:10746–10755. https://doi.org/10.1021/BI034541N

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Ho CT (2012) Flavour chemistry of methylglyoxal and glyoxal. Chem Soc Rev 41:4140–4149. https://doi.org/10.1039/C2CS35025D

    Article  CAS  PubMed  Google Scholar 

  13. Sudnitsyna MV, Gusev NB (2017) Methylglyoxal and small heat shock proteins. Biochemistry (Mosc) 82:751–759. https://doi.org/10.1134/S000629791707001X

    Article  CAS  PubMed  Google Scholar 

  14. Mir AR, Uddin M, Alam K, Ali A (2014) Methylglyoxal mediated conformational changes in histone H2A-generation of carboxyethylated advanced glycation end products. Int J Biol Macromol 69:260–266. https://doi.org/10.1016/J.IJBIOMAC.2014.05.057

    Article  CAS  PubMed  Google Scholar 

  15. Haik GM, Lo TWC, Thornalley PJ (1994) Methylglyoxal concentration and glyoxalase activities in the human lens. Exp Eye Res 59:497–500. https://doi.org/10.1006/EXER.1994.1135

    Article  CAS  PubMed  Google Scholar 

  16. Ahmed N, Thornalley PJ, Dawczynski J et al (2003) Methylglyoxal-derived hydroimidazolone advanced glycation end-products of human lens proteins. Invest Ophthalmol Vis Sci 44:5287–5292. https://doi.org/10.1167/IOVS.03-0573

    Article  PubMed  Google Scholar 

  17. Nemet I, Vikić-Topić D, Varga-Defterdarović L (2004) Spectroscopic studies of methylglyoxal in water and dimethylsulfoxide. Bioorg Chem 32:560–570. https://doi.org/10.1016/J.BIOORG.2004.05.008

    Article  CAS  PubMed  Google Scholar 

  18. Wilker SC, Chellan P, Arnold BM, Nagaraj RH (2001) Chromatographic quantification of argpyrimidine, a methylglyoxal-derived product in tissue proteins: comparison with pentosidine. Anal Biochem 290:353–358. https://doi.org/10.1006/ABIO.2001.4992

    Article  CAS  PubMed  Google Scholar 

  19. Ciriminna R, Fidalgo A, Ilharco LM, Pagliaro M (2018) Dihydroxyacetone: an updated insight into an important bioproduct. ChemistryOpen 7:233. https://doi.org/10.1002/OPEN.201700201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Daou M, Faulds CB (2017) Glyoxal oxidases: their nature and properties. World J Microbiol Biotechnol 33:1–11. https://doi.org/10.1007/S11274-017-2254-1/FIGURES/3

    Article  CAS  Google Scholar 

  21. Treibmann S, Spengler F, Degen J et al (2019) Studies on the formation of 3-deoxyglucosone- and methylglyoxal-derived hydroimidazolones of creatine during Heat treatment of meat. J Agric Food Chem. https://doi.org/10.1021/ACS.JAFC.9B01243/SUPPL_FILE/JF9B01243_SI_001.PDF

    Article  PubMed  Google Scholar 

  22. Nagaraj RH, Sady C (1996) The presence of a glucose-derived Maillard reaction product in the human lens. FEBS Lett 382:234–238. https://doi.org/10.1016/0014-5793(96)00142-1

    Article  CAS  PubMed  Google Scholar 

  23. Chellan P, Nagaraj RH (1999) Protein crosslinking by the Maillard reaction: dicarbonyl-derived imidazolium crosslinks in aging and diabetes. Arch Biochem Biophys 368:98–104. https://doi.org/10.1006/ABBI.1999.1291

    Article  CAS  PubMed  Google Scholar 

  24. Shipanova IN, Glomb MA, Nagaraj RH (1997) Protein modification by methylglyoxal: chemical nature and synthetic mechanism of a major fluorescent adduct. Arch Biochem Biophys 344:29–36. https://doi.org/10.1006/ABBI.1997.0195

    Article  CAS  PubMed  Google Scholar 

  25. Seidler NW, Kowalewski C (2003) Methylglyoxal-induced glycation affects protein topography. Arch Biochem Biophys 410:149–154. https://doi.org/10.1016/S0003-9861(02)00662-8

    Article  CAS  PubMed  Google Scholar 

  26. Figueira Bento C, Marques F, Fernandes R, Pereira P (2010) Methylglyoxal alters the function and stability of critical components of the protein quality control. PloS One. https://doi.org/10.1371/journal.pone.0013007

    Article  Google Scholar 

  27. Biswas A, Miller AG, Oya-Ito T et al (2006) Effect of site-directed mutagenesis of methylglyoxal-modifiable arginine residues on the structure and chaperone function of human alphaa-crystallin. Biochemistry 45:4569–4577

    Article  CAS  PubMed  Google Scholar 

  28. Ahmed A, Shamsi A, Khan MS et al (2018) Methylglyoxal induced glycation and aggregation of human serum albumin: biochemical and biophysical approach. Int J Biol Macromol 113:269–276. https://doi.org/10.1016/J.IJBIOMAC.2018.02.137

    Article  CAS  PubMed  Google Scholar 

  29. Schalkwijk CG, Stehouwer CDA (2020) Methylglyoxal, a highly reactive dicarbonyl compound, in diabetes, its vascular complications, and other age-related diseases. Physiol Rev 100:407–461. https://doi.org/10.1152/PHYSREV.00001.2019

    Article  CAS  PubMed  Google Scholar 

  30. Satish Kumar M, Mrudula T, Mitra N, Bhanuprakash Reddy G (2004) Enhanced degradation and decreased stability of eye lens alpha-crystallin upon methylglyoxal modification. Exp Eye Res 79:577–583. https://doi.org/10.1016/J.EXER.2004.07.003

    Article  CAS  PubMed  Google Scholar 

  31. Ahmed N, Dobler D, Dean M, Thornalley PJ (2005) Peptide mapping identifies hotspot site of modification in human serum albumin by methylglyoxal involved in ligand binding and esterase activity. J Biol Chem 280:5724–5732. https://doi.org/10.1074/JBC.M410973200

    Article  CAS  PubMed  Google Scholar 

  32. Dobler D, Ahmed N, Song L et al (2006) Increased dicarbonyl metabolism in endothelial cells in hyperglycemia induces anoikis and impairs angiogenesis by RGD and GFOGER motif modification. Diabetes 55:1961–1969. https://doi.org/10.2337/DB05-1634

    Article  CAS  PubMed  Google Scholar 

  33. Thornalley PJ (2008) Protein and nucleotide damage by glyoxal and methylglyoxal in physiological systems–role in ageing and disease. Drug Metabol Drug Interact 23:125–150. https://doi.org/10.1515/DMDI.2008.23.1-2.125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Westwood ME, Thornalley PJ (1995) Molecular characteristics of methylglyoxal-modified bovine and human serum albumins. Comparison with glucose-derived advanced glycation endproduct-modified serum albumins. J Protein Chem 14:359–372. https://doi.org/10.1007/BF01886793

    Article  CAS  PubMed  Google Scholar 

  35. Thornalley PJ, Battah S, Ahmed N et al (2003) Quantitative screening of advanced glycation endproducts in cellular and extracellular proteins by tandem mass spectrometry. Biochem J 375:581–592. https://doi.org/10.1042/BJ20030763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ahmed MU, Brinkmann Frye E, Degenhardt TP et al (1997) N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem J 324(Pt 2):565–570. https://doi.org/10.1042/BJ3240565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Bieme KM, Alexander Fried D, Lederer MO (2002) Identification and quantification of major maillard cross-links in human serum albumin and lens protein. Evidence for glucosepane as the dominant compound. J Biol Chem 277:24907–24915. https://doi.org/10.1074/JBC.M202681200

    Article  Google Scholar 

  38. Srivastava K, Chaves JM, Srivastava OP, Kirk M (2008) Multi-crystallin complexes exist in the water-soluble high molecular weight protein fractions of aging normal and cataractous human lenses. Exp Eye Res 87:356–366. https://doi.org/10.1016/j.exer.2008.07.001

    Article  CAS  PubMed  Google Scholar 

  39. Biswas A, Lewis S, Wang B et al (2008) Chemical modulation of the chaperone function of human alphaa-crystallin. J Biochem 144:21–32. https://doi.org/10.1093/JB/MVN037

    Article  CAS  PubMed  Google Scholar 

  40. Rabbani N, Thornalley PJ (2014) Measurement of methylglyoxal by stable isotopic dilution analysis LC–MS/MS with corroborative prediction in physiological samples. Nat Protoc. https://doi.org/10.1038/nprot.2014.129

    Article  PubMed  Google Scholar 

  41. Bierhaus A, Fleming T, Stoyanov S et al (2012) Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy. Nat Med 18:6. https://doi.org/10.1038/nm.2750

    Article  CAS  Google Scholar 

  42. Rabbani N, Thornalley PJ (2014) Dicarbonyl proteome and genome damage in metabolic and vascular disease. Biochem Soc Trans 42:425–432. https://doi.org/10.1042/BST20140018

    Article  CAS  PubMed  Google Scholar 

  43. Dhar A, Desai K, Liu J, Wu L (2009) Methylglyoxal, protein binding and biological samples: are we getting the true measure? J Chromatogr B 877:1093–1100. https://doi.org/10.1016/J.JCHROMB.2009.02.055

    Article  CAS  Google Scholar 

  44. Dakin HD, Dudley HW (1913) The interconversion of α-amino-acids, α-hydroxy-acids and α-ketonic aldehydes. part II. J Biol Chem 15:127–143. https://doi.org/10.1016/S0021-9258(18)88548-9

    Article  CAS  Google Scholar 

  45. Kalapos MP (1994) Methylglyoxal toxicity in mammals. Toxicol Lett 73:3–24. https://doi.org/10.1016/0378-4274(94)90184-8

    Article  CAS  PubMed  Google Scholar 

  46. Kalapos MP, Schaff Z, Garzó T et al (1991) Accumulation of phenols in isolated hepatocytes after pretreatment with methylglyoxal. Toxicol Lett 58:181–191. https://doi.org/10.1016/0378-4274(91)90172-3

    Article  CAS  PubMed  Google Scholar 

  47. Wolstenholme GEW, Fitzsimons DW, Whelan J (2008) Submolecular biology and cancer. Submol Biol Cancer. https://doi.org/10.1002/9780470720493

    Article  Google Scholar 

  48. Apple MA, Greenberg DM (1967) Inhibition of cancer growth in mice by a normal metabolite. Life Sci 6:2157–2160. https://doi.org/10.1016/0024-3205(67)90237-8

    Article  CAS  PubMed  Google Scholar 

  49. Ahmed N (2005) Advanced glycation endproducts—role in pathology of diabetic complications. Diabetes Res Clin Pract 67:3–21. https://doi.org/10.1016/J.DIABRES.2004.09.004

    Article  CAS  PubMed  Google Scholar 

  50. Angeloni C, Zambonin L, Hrelia S (2014) Role of methylglyoxal in alzheimer’s disease. Biomed Res Int. https://doi.org/10.1155/2014/238485

    Article  PubMed  PubMed Central  Google Scholar 

  51. de Almeida GRL, Szczepanik JC, Selhorst I et al (2023) The expanding impact of methylglyoxal on behavior-related disorders. Prog Neuropsychopharmacol Biol Psychiatry 120:110635. https://doi.org/10.1016/J.PNPBP.2022.110635

    Article  PubMed  Google Scholar 

  52. Biessels GJ, Staekenborg S, Brunner E et al (2006) Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol 5:64–74. https://doi.org/10.1016/S1474-4422(05)70284-2

    Article  PubMed  Google Scholar 

  53. Bouhassira D, Lantéri-Minet M, Attal N et al (2008) Prevalence of chronic pain with neuropathic characteristics in the general population. Pain 136:380–387. https://doi.org/10.1016/J.PAIN.2007.08.013

    Article  PubMed  Google Scholar 

  54. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426:6968. https://doi.org/10.1038/nature02263

    Article  CAS  Google Scholar 

  55. Chaudhuri J, Bains Y, Guha S et al (2018) The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell Metab 28:337–352. https://doi.org/10.1016/J.CMET.2018.08.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Ott C, Jacobs K, Haucke E et al (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429. https://doi.org/10.1016/J.REDOX.2013.12.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Irshad Z, Xue M, Ashour A et al (2019) Activation of the unfolded protein response in high glucose treated endothelial cells is mediated by methylglyoxal. Sci Rep. https://doi.org/10.1038/s41598-019-44358-1

    Article  PubMed  PubMed Central  Google Scholar 

  58. Rabbani N, Xue M, Thornalley PJ (2020) Dicarbonyl stress and the glyoxalase system in oxidative stress: eustress and distress. Academic Press, pp. 759–777. https://doi.org/10.1016/B978-0-12-818606-0.00036-5

  59. Lo TWC, Westwood ME, Mclellan AC et al (1994) Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. J Biol Chem 269:32299–32305. https://doi.org/10.1016/S0021-9258(18)31635-1

    Article  CAS  PubMed  Google Scholar 

  60. Vander DL et al (1992) Reduction of trioses by NADPH-dependent aldo-keto reductases. Aldose reductase, methylglyoxal, and diabetic complications. J Biol Chem 267:4364–4369. https://doi.org/10.1016/S0021-9258(18)42844-X

    Article  Google Scholar 

  61. Booth AA, Khalifah RG, Todd P, Hudson BG (1997) In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). J Biol Chem 272:5430–5437. https://doi.org/10.1074/jbc.272.9.5430

    Article  CAS  PubMed  Google Scholar 

  62. Kalapos MP (2008) The tandem of free radicals and methylglyoxal. Chem Biol Interact 171:251–271. https://doi.org/10.1016/J.CBI.2007.11.009

    Article  CAS  PubMed  Google Scholar 

  63. Lai SWT, Lopez Gonzalez EDJ, Zoukari T et al (2022) Methylglyoxal and its adducts: induction, repair, and association with disease. Chem Res Toxicol 35:1720–1746. https://doi.org/10.1021/ACS.CHEMRESTOX.2C00160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Riboulet-Chavey A, Pierron A, Durand I et al (2006) Methylglyoxal impairs the insulin signaling pathways independently of the formation of intracellular reactive oxygen species. Diabetes 55:1289–1299. https://doi.org/10.2337/DB05-0857

    Article  CAS  PubMed  Google Scholar 

  65. Ng Y, Ramm G, Lopez JA, James DE (2008) Rapid activation of Akt2 is sufficient to stimulate GLUT4 translocation in 3T3-L1 adipocytes. Cell Metab 7:348–356. https://doi.org/10.1016/J.CMET.2008.02.008

    Article  CAS  PubMed  Google Scholar 

  66. Zhang W, Thompson BJ, Hietakangas V, Cohen SM (2011) MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in drosophila. PLoS Genet 7:e1002429. https://doi.org/10.1371/JOURNAL.PGEN.1002429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Marko AJ, Miller RA, Kelman A, Frauwirth KA (2010) Induction of glucose metabolism in stimulated T lymphocytes is regulated by mitogen-activated protein kinase signaling. PLoS ONE 5. doi: 10.1371/JOURNAL.PONE.0015425.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  68. Han Y, Randell E, Vasdev S et al (2007) Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with type 1 diabetes. Mol Cell Biochem 305:123–131. https://doi.org/10.1007/S11010-007-9535-1

    Article  CAS  PubMed  Google Scholar 

  69. Kong X, Ma MZ, Huang K et al (2014) Increased plasma levels of the methylglyoxal in patients with newly diagnosed type 2 diabetes 2. J Diabetes 6:535–540. https://doi.org/10.1111/1753-0407.12160

    Article  CAS  PubMed  Google Scholar 

  70. Bellier J, Nokin MJ, Lardé E et al (2019) Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer. Diabetes Res Clin Pract 148:200–211. https://doi.org/10.1016/J.DIABRES.2019.01.002

    Article  CAS  PubMed  Google Scholar 

  71. Allaman I, Bélanger M, Magistretti PJ (2015) Methylglyoxal, the dark side of glycolysis. Front Neurosci 9:123680. https://doi.org/10.3389/FNINS.2015.00023/BIBTEX

    Article  Google Scholar 

  72. Kumar PA, Kumar MS, Reddy GB (2007) Effect of glycation on alpha-crystallin structure and chaperone-like function. Biochem J 408:251–258. https://doi.org/10.1042/BJ20070989

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Harding J (1991) Biochemistry, epidemiology, and pharmacology. Cataract

    Google Scholar 

  74. Bloemendal H, De Jong W, Jaenicke R et al (2004) Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol 86:407–485. https://doi.org/10.1016/j.pbiomolbio.2003.11.012

    Article  CAS  PubMed  Google Scholar 

  75. Sharma KK, Santhoshkumar P (2009) Lens aging: effects of crystallins. Biochim Biophys Acta 1790:1095–1108. https://doi.org/10.1016/J.BBAGEN.2009.05.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Raju M, Santhoshkumar P, Sharma KK (2016) Alpha-crystallin-derived peptides as therapeutic chaperones. Biochim Biophys Acta 1860:246–251. https://doi.org/10.1016/J.BBAGEN.2015.06.010

    Article  CAS  PubMed  Google Scholar 

  77. Nagaraj RH, Nahomi RB, Mueller NH et al (2016) Therapeutic potential of α-crystallin. Biochim Biophys Acta 1860:252–257. https://doi.org/10.1016/J.BBAGEN.2015.03.012

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, India for extending all the facilities to carry out the work.

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  1. Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, India

    Nainika Prashant Kotian, Anusha Prabhu, Tenzin Tender & Hariharapura Raghu Chandrashekar

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RCH conceptualized and designed the project. TT, NK, and, AP performed the literature search, analysis and wrote the manuscript. RCH, edited the manuscript.

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Kotian, N.P., Prabhu, A., Tender, T. et al. Methylglyoxal Induced Modifications to Stabilize Therapeutic Proteins: A Review. Protein J 43, 39–47 (2024). https://doi.org/10.1007/s10930-023-10166-w

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