Catalysis of imido group hydrolysis in a maleimide conjugate

Bioorg Med Chem Lett. 2007 Nov 15;17(22):6286-9. doi: 10.1016/j.bmcl.2007.09.002. Epub 2007 Sep 7.


Maleimides are often used for biomolecular conjugation with thiols. An underappreciated aspect of the imido group in a maleimide conjugate is its susceptibility to spontaneous hydrolysis, resulting in undesirable heterogeneity. Here, a chromophoric maleimide is used to demonstrate that both molybdate and chromate catalyze the hydrolysis of an imido group near neutral pH. Tungstate and 4-(dimethylamino)pyridine are less effective as catalysts. This work reveals a new mode of chemical reactivity for molybdate and chromate, and provides a strategy for decreasing the heterogeneity of bioconjugates derived from maleimides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Catalysis
  • Chromates / chemistry
  • Hydrogen-Ion Concentration
  • Imides / chemistry*
  • Maleimides / chemistry*
  • Molecular Structure
  • Molybdenum / chemistry


  • Chromates
  • Imides
  • Maleimides
  • molybdate
  • maleimide
  • Molybdenum