Bromomaleimides: new reagents for the selective and reversible modification of cysteine

Abstract

Bromomaleimides react rapidly and selectively with cysteine to afford thiomaleimides which can be cleaved with a phosphine to regenerate the cysteine or treated with a base to afford dehydroalanine.

Easy Access to 1H‐Pyrrolo[3′,4′:5,6]pyrido[2,3‐d]pyrimidine‐2,4,6,8(3H,7H)‐tetraone and Selectively N7‐Substituted Analogues through Key Synthons

“…However, no reaction occurred when carbaldehyde 4 and maleimide (12) were heated to reflux in tetrahydrofuran (THF). Under microwave irradiation in the same solvent, several products were obtained.…”

“…The synthesis of aminomaleimide (9) was realized in two steps and 61 % overall yield from bromomaleimide (11) by reaction with sodium azide in dimethylformamide (DMF) at room temperature and catalytic reduction of resulting azido derivative 14 (Scheme 3). Bromomale-imide (11) was prepared by dibromination of maleimide (12) and subsequent elimination of hydrobromhydric acid in accordance with the method previously described by Baker. [12] However, replacement of chloroform by dichloromethane in the first step and modification of the work up allowed us to improve the yield to 86 % from 59 %.…”

“…Bromomale-imide (11) was prepared by dibromination of maleimide (12) and subsequent elimination of hydrobromhydric acid in accordance with the method previously described by Baker. [12] However, replacement of chloroform by dichloromethane in the first step and modification of the work up allowed us to improve the yield to 86 % from 59 %. With the aminomaleimide in hand, it was used in the three-component reaction with paraformaldehyde (8) and barbituric acid (7).…”

Use of a next generation maleimide in combination with THIOMAB™ antibody technology delivers a highly stable, potent and near homogeneous THIOMAB™ antibody-drug conjugate (TDC)

“…21 We have also introduced monobromomaleimides (MBMs) as fast reagents for conjugation to single cysteines. 53 We envisaged introducing a glycine spacer between the MBM and the valinecitrulline self-immolative linker carrying monomethyl auristatin E (vc-PABC-MMAE) to enhance hydrolysis of the resulting maleimide conjugate. Conjugation of this reagent to the THI-OMAB™ antibody should create a highly stable and homogeneous TDC with a DAR of ca.…”

Reversible surface functionalisation of emulsion-templated porous polymers using dithiophenol maleimide functional macromolecules

“…15,16 The unreacted thiols can be exploited as reactive 'handles' with which to introduce functionality onto the polyHIPE surface using a wide range of chemical transformations via the thiolMichael addition click reaction. 17 Recent studies have shown that dibromomaleimides (DBMs) are able to conjugate to cysteine residues 18 and to re-bridge peptides containing disulfide bonds following in situ reduction. 19 Dithiophenol maleimides (DTMs) have also been demonstrated as highly efficient and rapid re-bridging agents for the disulfide containing peptides.…”