Spiroheptadiene Reagents to React with Maleimide to Modify Antibodies

N⁶-[(Spiro[2.4]hept-4,6-dien-1-ylmethoxy)carbonyl]-L-lysine (1) enables the site-specific modification of proteins, making it useful for the preparation of homogeneous antibody-drug conjugates (ADCs).¹⁾ The spiroheptadiene (SCp) moiety of 1, introduced into a specific site of the protein by genetic code expansion, reacts with the maleimide moiety at a rate of 1.8-5.4 M^-1 s^-1 with the Diels-Alder reaction to form a 6-membered ring.²⁾ ADCs obtained by reacting 1-incorporated antibodies with drug-conjugated maleimides exhibit better stability and efficacy than cysteine-maleimide conjugates both in mouse serum and in vivo.
We also offer 4-nitrophenyl spiro[2.4]hepta-4,6-dien-1-ylmethyl carbonate (2) as a reagent to introduce SCp moiety.

References

• 1) Click chemistry in the synthesis of antibody-drug conjugate
  • R. Dudchak, M. Podolak, S. Holota, O. Szewczyk-Roszczenko, P. Roszczenko, A. Bielawska, R. Lesyk, K. Bielawski, Bioorg. Chem. 2024, 143, 106982.
• 2) A Reactive Antibody Platform for One-Step Production of Antibody-Drug Conjugates through a Diels-Alder Reaction with Maleimide
  • A. H. St. Amant, F. Huang, J. Lin, D. Lemen, C. Chakiath, S. Mao, C. Fazenbaker, H. Zhong, J. Harper, W. Xu, N. Patel, L. Adams, B. Vijayakrishnan, P. W. Howard, M. Marelli, H. Wu, C. Gao, J. Read de Alaniz, R. J. Christie, Bioconjugate Chem. 2019, 30, 2340.

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