Maleimide  Maleimide is a chemical compound with the formula H2C2(CO)2NH (see diagram). This unsaturated imide is an important building block in organic synthesis. The name is a contraction of maleic acid and imide, the -C(O)NHC(O)- functional group. Maleimides also describes a "class" of derivatives of the parent maleimide where the N"H" group is replaced with alkyl or aryl groups such as a methyl or phenyl, respectively. The substituent can also be a small molecule (such as biotin, a fluorescent dye, an oligosaccharide a nucleic acid), a reactive group, or a synthetic polymer such as polyethylene glycol. Human hemoglobin chemically modified with maleimide-polyethylene glycol is a blood substitute called MP4. Maleimide and its derivatives are prepared from maleic anhydride by treatment with amines followed by dehydration. A special feature of the reactivity of maleimides is their susceptibility to additions across the double bond either by Michael additions or via Diels-Alder reactions. Bismaleimides are a class of compounds with two maleimide groups connected by the nitrogen atoms via a linker, and are used as crosslinking reagents in thermoset polymer chemistry. Compounds containing a maleimide group linked with another reactive group, such as an activated N-hydroxysuccinimide ester, are called maleimide heterobifunctional reagents (for example, see SMCC reagent). Only a handful of natural maleimides – exemplified by the cytotoxic showdomycin from "Streptomyces showdoensis", and pencolide from "Pe. multicolor" – have been reported. Farinomalein was first isolated in 2009 from the entomopathogenic fungus "Isaria farinosa" ("Paecilomyces farinosus") – source H599 (Japan). Maleimide-mediated methodologies are among the most used in bioconjugation. Due to exceptionally fast reaction rates and significantly high selectivity towards cysteine residues in proteins, a large variety of maleimide heterobifunctional reagents are used for the preparation of targeted therapeutics, assemblies for studying proteins in their biological context, protein-based microarrays, or proteins immobilisation. For instance, emerging promising targeted drug therapies, antibody-drug conjugates, are constituted of three main components: a monoclonal antibody, a cytotoxic drug, and a linker molecule often containing a maleimide group, which binds the drug and the antibody.