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site specific conjugation on proteins

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What are the latest trends in site specific conjugations methods on proteins?

Protein Chemistry
Peptide Chemistry
Fluoropolymers
Philippe Cronet
12 days ago

2 answers

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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

  1. Antibody Drug conjugates with drugs and linkers
  2. Antibody and target selection
  3. Anti-CD30 monoclonal antibody conjugated to the highly cytotoxic drug monomethylauristatin E (MMAE) via modification of native cysteine side chain thiols.[1]
  4. Site-specific protein modification via a novel cysteine-containing fusion tag (Cys-tag)[2] or cysteine-engineered antibodies.[3]
  5. Modified aptamers[4]
  6. Sortase variants[5, 6]
  7. Oxime conjugation[7]
  8. Microbial Transglutaminase[8]
  9. Incorporation of bioorthogonal functionalities[9]
  10. Transglutaminase-Catalyzation[10]
  11. PEGylation[11]

References

  1. Behrens, C.R. and B. Liu, Methods for site-specific drug conjugation to antibodies. mAbs, 2014. 6(1): p. 46-53.
  2. 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.
  3. 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.
  4. Wang, R., et al., Using modified aptamers for site specific protein-aptamer conjugations. Chemical Science, 2016. 7(3): p. 2157-2161.
  5. Chen, L., et al., Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency. 2016. 6: p. 31899.
  6. 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.
  7. 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.
  8. 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.
  9. Rashidian, M., J.K. Dozier, and M.D. Distefano, Enzymatic Labeling of Proteins: Techniques and Approaches. Bioconjugate Chemistry, 2013. 24(8): p. 1277-1294.
  10. 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.
  11. 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.
Dr. Ahson Jabbar Shaikh
12 days ago
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Nice overview. And I agree on entry 1, that I see as THE hot topic. More specific the use of Click Chemistry. Activation by e.g. converting a biomolecule to the coresponding azide. binding dyes and drugs by a covalent bond.

Oskar Middel
12 days ago

Have some input?