- Cys–Cys and Cys–Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents
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Easy access to a wide range of structurally diverse stapled peptides is crucial for the development of inhibitors of protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents for two-component cysteine-cysteine and cysteine-lysine stapling yielding structurally diverse thioalkyne linkers. This stapling method works with unprotected natural amino acid residues and does not require pre-functionalization or metal catalysis. The products are stable to purification and isolation. Post-stapling modification can be accessed via amidation of an activated ester, or via cycloaddition onto the formed thioalkyne group. Increased helicity and binding affinity to MDM2 was obtained for a i,i+7 stapled peptide.
- Ceballos, Javier,Grinhagena, Elija,Sangouard, Gontran,Heinis, Christian,Waser, Jerome
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supporting information
p. 9022 - 9031
(2021/03/16)
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- AROMATIC CARBOXYLIC ACIDS, ACID HALIDES THEREOF AND PROCESSES FOR PREPARING BOTH
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A novel aromatic carboxylic acid useful as a material for macromolecular compounds and, in particular, for polycondensed macromolecular compounds exhibiting excellent heat resistance, an acid halide derivative thereof and a process for producing these compounds are disclosed. The aromatic carboxylic acid and the acid halide derivative thereof have structures represented general formulae (1) and (2), respectively, and can be efficiently produced from a dialkyl ester derivative of isophthalic acid and an acetylene derivative in accordance with the disclosed process comprising specific steps. In the above formulae, A represents:- C≡C-R1 or (R1 represents hydrogen atom, an alkyl group or an aromatic group, R2 represents an alkyl group or an aromatic group) and X represents a halogen atom.
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