site specific conjugation on proteins
Although I am not expert in this field, but quick literature yielded following results.(This is not elaborate literature search)
latest trends in site specific conjugations methods on proteins
- Antibody Drug conjugates with drugs and linkers
- Antibody and target selection
- Anti-CD30 monoclonal antibody conjugated to the highly cytotoxic drug monomethylauristatin E (MMAE) via modification of native cysteine side chain thiols.
- Site-specific protein modification via a novel cysteine-containing fusion tag (Cys-tag) or cysteine-engineered antibodies.
- Modified aptamers
- Sortase variants[5, 6]
- Oxime conjugation
- Microbial Transglutaminase
- Incorporation of bioorthogonal functionalities
- Behrens, C.R. and B. Liu, Methods for site-specific drug conjugation to antibodies. mAbs, 2014. 6(1): p. 46-53.
- Backer, M.V., et al., Cysteine-Containing Fusion Tag for Site-Specific Conjugation of Therapeutic and Imaging Agents to Targeting Proteins, in Peptide-Based Drug Design, L. Otvos, Editor. 2008, Humana Press: Totowa, NJ. p. 275-294.
- Shinmi, D., et al., One-Step Conjugation Method for Site-Specific Antibody–Drug Conjugates through Reactive Cysteine-Engineered Antibodies. Bioconjugate Chemistry, 2016. 27(5): p. 1324-1331.
- Wang, R., et al., Using modified aptamers for site specific protein-aptamer conjugations. Chemical Science, 2016. 7(3): p. 2157-2161.
- Chen, L., et al., Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency. 2016. 6: p. 31899.
- Glasgow, J.E., M.L. Salit, and J.R. Cochran, In Vivo Site-Specific Protein Tagging with Diverse Amines Using an Engineered Sortase Variant. Journal of the American Chemical Society, 2016. 138(24): p. 7496-7499.
- Agten, S.M., P.E. Dawson, and T.M. Hackeng, Oxime conjugation in protein chemistry: from carbonyl incorporation to nucleophilic catalysis. Journal of Peptide Science, 2016. 22(5): p. 271-279.
- Wakabayashi, R., et al., Protein-Grafted Polymers Prepared Through a Site-Specific Conjugation by Microbial Transglutaminase for an Immunosorbent Assay. Biomacromolecules, 2017. 18(2): p. 422-430.
- Rashidian, M., J.K. Dozier, and M.D. Distefano, Enzymatic Labeling of Proteins: Techniques and Approaches. Bioconjugate Chemistry, 2013. 24(8): p. 1277-1294.
- Lin, C.-W. and A.Y. Ting, Transglutaminase-Catalyzed Site-Specific Conjugation of Small-Molecule Probes to Proteins in Vitro and on the Surface of Living Cells. Journal of the American Chemical Society, 2006. 128(14): p. 4542-4543.
- Nischan, N. and C.P.R. Hackenberger, Site-specific PEGylation of Proteins: Recent Developments. The Journal of Organic Chemistry, 2014. 79(22): p. 10727-10733.
Proteins play myriads of role such as (i) providing structure, strength & stability, (ii) Cell signaling and regulate cellular/physiological activities, (iii)catalyzing reactions (Enzyme), (iv) storage & transport, (v) defend the body from external attack. Modifications of protein are used for studying structure and function relationships for in-vitro & in-vivo research. Protein modifications also find immense potential in therapeutic applications (targeted drug delivery using proteins such as hormones and antibodies that are naturally bear very high specificity for their target) and in diagnosis (Biosensors for cancer detection and maintenance). Protein bioconjugates can be synthesized by using chemical reactions, enzymatic reactions, or genetic engineering technologies. There are several tools for site specific modification of proteins that can be categories into three broad classes such as (i) Chemical modifications of proteins, (ii) Metabolic modifications, (iii) Post translational modifications. The purpose of all these reactions are to selectively install particular modifications on proteins for many biological and therapeutic applications.
The protein modification reactions in current use vary widely in their inherent site selectivity, overall yields and functional group compatibility. The recent trends to overcome the challenges in the existing methodologies for site specific conjugations on proteins will be found out from following most recent works going on across the globe. The antibody drug conjugates (ADCs) is one of the hot topics in protein conjugations
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