Swarupananda Mukherjee, Saumyakanti Giri, Sohini Bera, Sharanya Mukherjee, Shankha Dey, Niladri Sekhar Roy
Swarupananda.firstname.lastname@example.org , email@example.com
Swarupananda Mukherjee*, Saumyakanti Giri, Sohini Bera, Sharanya Mukherjee, Shankha Dey, Niladri Sekhar Roy
NSHM Knowledge Campus Kolkata – Group of Institutions, Department of Pharmaceutical Technology, 124, B L Saha Road, Kolkata – 700053.
Volume - 14,
Issue - 9,
Year - 2021
The protein degradation is a well-controlled, highly selective mechanism for intracellular protein degradation and its turnover. There are several proteins in our body but among them some goes for degradation at a time. Proteins which are going to be degraded are identified by a 76 amino acid polypeptide known as ubiquitin and the process is known as ubiquitination. Ubiquitation means the attachment of many ubiquitin molecules to the target protein molecule that need to be broken down. During the ubiquitination procedure iso peptide bonds are formed. And these iso peptide bonds are formed between the nitrogen molecule of the lysine residue from the target protein and the carbon molecule of the ubiquitin molecule. Through this endogenous ubiquitin-proteasome machinery, disease responsible proteins can be permanently removed. Energy is required for this process and that’s why ATP is employed in this process. This targeted protein degradation plays a very crucial role for cancer and other diseases. Through this review we just enlighten the significant points if the targeted protein degradation and its significance.
Cite this article:
Swarupananda Mukherjee, Saumyakanti Giri, Sohini Bera, Sharanya Mukherjee, Shankha Dey, Niladri Sekhar Roy. Targeted Protein Degradation: Current Status and Future Prospects. Research Journal of Pharmacy and Technology. 2021; 14(9):5047-0. doi: 10.52711/0974-360X.2021.00880
Swarupananda Mukherjee, Saumyakanti Giri, Sohini Bera, Sharanya Mukherjee, Shankha Dey, Niladri Sekhar Roy. Targeted Protein Degradation: Current Status and Future Prospects. Research Journal of Pharmacy and Technology. 2021; 14(9):5047-0. doi: 10.52711/0974-360X.2021.00880 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2021-14-9-94
1. Philipp M C, Craig M C. Targeted Protein Degradation: from Chemical Biology to Drug Discovery. Cell Chem Biol. 2017; 23; 3(8): 830–838.
2. Komander D, Rape M. The ubiquitin code. Annu Rev Biochem. 2012; 81: 203–229.
3. Sakamoto KM, Kim KB, Kumagai A, Mercurio F, Crews CM, Deshaies RJ. Protacs: chimeric molecules that target proteins to the Skp1‐Cullin‐F box complex for ubiquitination and degradation. Proc Natl Acad Sci. 2001; 98:8554‐8559.
4. Mansour MA. Ubiquitination: friend and foe in cancer. Int J Biochem Cell Biol. 2018; 101:80‐93
5. Pickart CM, Eddins MJ. Ubiquitin: structures, functions, mechanisms. Biochim Biophys Acta. 2004;1695: 55–72.
6. Surendra KN, Gopal LK, Rakesh N, Vikramdeep M. Role of Mdm2 Cascade in Human Cancers. Research J. Pharm. and Tech. 2017; 10(7): 2236-2242.
7. Meena C, Shiny G, Kumaran S, Pallavi G, Rajasekar D. Molecular Docking of 3, 5, 7-Trihydroxy-2-(4-Hydroxy-3-Methoxyphenyl)-4h-Chromen-4-One Derivatives Against Il-6 for Rheumatoid Arthritis. Asian J. Research Chem. 2011; 4(8):1254-1257.
8. Ogugua VN, Emmanuel TN., Enechi OC. Effect of Vitamin E-stored Experimental Blood Samples on Malondialdehyde and Protein Concentration. Asian J. Research Chem. 2012;5(6):765-766.
9. Sravani M, Duganath N, Deepak RG, Sandeep RCH. Insilico Analysis and Docking of Imatinib Derivatives Targeting BCR-ABL Oncoprotein for Chronic Myeloid Leukemia. Asian J. Research Chem. 2012;5(1):153-158.
10. Swati K, Rajani N, Chaitrali P, Rohit S, Priyanka J, Bhakti C. Selenium as an Antioxidant: A Review. Asian J. Research Chem. 2013;6(3):278-285.
11. Deshaies RJ, Joazeiro CAP. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399–434.
12. Berndsen CE, Wolberger C. New insights into ubiquitin E3 ligase mechanism. Nat Struct Mol Biol.2014; 21: 301–307.
13. Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA, Orth A, Chanda SK, Batalov S, Joazeiro CAP. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle’s dynamics and signaling. Plos ONE. 2008;3(1): e1487.
14. Hopkins AL, Groom CR. The druggable genome. Nat Rev Drug Discov. 2002; 1: 727–730.
15. Paiva SL, Crews CM. Targeted protein degradation: elements of PROTAC design. Curr Opin Chem Biol. 2019;50:111-119.
16. Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007; 450: 1001–1009.
17. Surade S, Blundell TL. Structural biology and drug discovery of difficult targets: the limits of ligandability. Chem Biol. 2012; 19: 42–50.
18. Sameena M, Harpreet P, Tanveer IS, Atanu SR. Determination of Protein Binding Affinities and Investigation into the Antimicrobial Activities of Cu(II), Co(II) and Ni(II) Mixed Ligand Complexes. Asian J. Research Chem 2015; 8(2):99-107.
19. Shlini. P, Shahzia Khan, Shivangi. Protein Fractionation and its Invitro Hemagglutinating Activity of Star anise Extracts. Asian J. Research Chem. 2017; 10(3):305-308.
20. Sushant S Dhavale, AV Bhosle, SR Hardikar, Tushar R Kotkar. Significance of P-Glycoproteins as a Transporter System. Research J. Pharm. and Tech. 2008;1(4):298-309.
21. Srikanth J, Muralidharan P, Antihyperlipidemic activity of Sapindus emarginatus in Triton WR-1339 induced albino rats. Research J. Pharm. and Tech. 2009;2(2):319-323.
22. Rajesh VB, Syeda RN, Nivethithai P, Areefulla SH. Approaches and Challenges of Protein and Peptide Drug Delivery Systems. Research J. Pharm. and Tech. 2010;3(2):379-384.
23. Lazo JS, Sharlow ER. Drugging undruggable molecular cancer targets. Annu Rev Pharmacol Toxicol. 2016; 56: 23–40.
24. Toure M, Crews CM. Small-molecule PROTACs. New approaches to protein degradation. Angew Chem Int Ed. 2016; 55: 1966–1973.
25. Bondeson DP, Crews CM. Targeted protein degradation by small molecules. Annu. Rev Pharmacol Toxicol. 2017;57: 107–123
26. Lai AC, Crews CM. Induced protein degradation: an emerging drug discovery paradigm. Nat Rev Drug Discov. 2017; 16: 101–114
27. Ottis P, Crews CM. Proteolysis-targeting chimeras. Induced protein degradation as a therapeutic strategy. ACS Chem Biol. 2017;12: 892–898.
28. An S, Fu L. Small-molecule PROTACs: An emerging and promising approach for the development of targeted therapy drugs, EBio Medicine. 2018; 36: 553–562.
29. Daniel P B, Craig M C. Targeted Protein Degradation by Small Molecules. Annual Reviews. 2017; 57: 187.
30. Hershko A. Roles of ubiquitin-mediated proteolysis in cell cycle control Curr Opin Cell Biol. 1997; 9: 788–799.
31. King RW, Deshaies RJ, Peters JM, Kirschner MW. How proteolysis drives the cell cycle. Science.1996;274(5293):1652-9.
32. Wang X, Luo H, Chen H, Duguid W, Wu J. Role of proteasomes in T cell activation and proliferation. J Immunol. 1998; 160: 788–801.
33. Orlowski RZ. The role of the ubiquitin-proteasome pathway in apoptosis. Cell Death Differ.1999;6(4):303-13.
34. Murray RZ, Norbury C. Proteasome inhibitors as anti-cancer agents. Anticancer Drugs. 2000; 11: 407–417.
35. Spataro V, Norbury C, Harris AL. The ubiquitin-proteasome pathway in cancer. Br J Cancer. 1998; 77: 448–455.