Maleimide bond formation

Figure 20.4 Reduction of the disulfide bonds within the hinge region of an IgG molecule produces half-anti-body molecules containing thiol groups. Reaction of these reduced antibodies with a maleimide-activated enzyme creates a conjugate through thioether bond formation.

Figure 21.13 Sulfo-SMCC may be used to activate antibody molecules for coupling to thiolated toxin components. An intact A-B toxin molecule can be modified to contain sulfhydryls by treatment with 2-iminothiolane. Thiolation with this reagent retains the cytotoxic properties of the toxin while generating a sulfhydryl for conjugation. Reaction of the thiolated toxin with the maleimide-activated antibody creates the immunotoxin through thioether bond formation.

There is only one other example of ribozyme-catalyzed carbon-carbon bond formation, and this also is a Diels-Alder reaction [13, 14]. The ribozymes isolated by the Eaton group accelerated the reaction of a tethered aliphatic diene with biotinylated maleimide approximately 800-fold, although no activity was observed toward the two free reactants. A second feature is that these ribozymes contain modified nucleotides and their activity depends on the presence of cupric ion. 

Covalently immobilized arrays are formatted by glycans with functionalized spacers that react with a complementary activated surface to form a covalent bond. Several different covalent interactions were reported to construct a specified glycan array. Amine chemistry and thiol chemistry are the two major methods to conjugate glycans to the reactive substrate in the array surface (Fig. 15.2). Thiol chemistry was first adapted by Injae Shin in 2002 to react with the maleimide functional group (Fig. 15.2a, b) [7,41 ]. Disulfide bond formation was then reported for the fabrication... 

Ribozyme-catalyzed reactions involving C-C bond formations have also been reported. Seelig and Jaschke (233) presented the in vitro selection of ribozyme catalysts for the Diels-Alder reaction between maleimide and anthracene, employing a 2 X lO -member library of 160-mer modified ONs (L28) with 120 randomized positions. The selection strategy used is shown in Fig. 10.40. Library L28 was prepared from the corresponding dsDNA sequences, and transcription initiation was performed in the presence of ternary complexes between guanosine monophosphate (10.57), PEG (10.58), and anthracene (10.59, step a. Fig. 10.40). The library obtained contained a 5 -anthracene-PEG appendage and was incubated with biotin-modified maleimide... 

Synthesis of showdomycin (4) by carbon-carbon bond formation between the D-ribose and maleimide subunits usually lacks stereospecificity and affords a mixture of 4 and its a anomer 94. Thus, reaction of unprotected D-ribose (90) with the maleimide-derived Wittig reagent 91 gave the unsaturated nucleoside 92 that was cyclized by the introduction and removal of a phenylseleno group to give a mixture of 4 and 94 the latter preponderated (84JOC3673 86JOC495) (Scheme 16). 

Arcyriacyanin-A, a green-blue pigment from Arcyria nutans was found to be isomeric with arcyriaflavin-A and exhibited mass and infrared spectra in accord with the presence of a maleimide moiety. In the H-n.m.r. spectrum the lack of signals from protons at the positions 2- and 4 - in the indole rings was taken to indicate bond formation... 

Self-replicating processes based on simple organic molecules may allow the transfer of chemical information to be passed on through the regio- and stereoselectivity of the template-catalyzed bond formation. A self-replicating system in which stereochemical information was transmitted faithfully to the formed template within the reactive ternary duplex was demonstrated using the 1,3-dipolar cycloaddition between nitrone 21 and maleimide 22 (Figure 10) ... 

Fig. 1 Schematic illustration of the various coupling methods that have been developed in order to post-functionalize liposomes, a Amine functionalization, b carboxylic acid functionalization, c aldehyde functionalization, d hydrazine functionalization, e maleimide ftmctionalization, f thiol functionalization, g thiol functionalization (disulfide bond formation), h bromoacetyl functionalization, i cysteine functionalization, j cyanur functionalization, kp-nitrophenylcarbonyl functionalization, I alkyne functionalization, m triphosphine functionalization...

Abstract The transport mechanism of the bovine heart mitochondrial ADP/ATP carrier was studied using submitochondrial particles. The modifications of the cysteine residues of the carrier by the SH-reagents eosin-5-maleimide (EMA) and Af-ethyhnaleimide (NEM), and disulfide bond formation between these cysteine residues catalyzed by copper-o-phenanthroline (Cu(OP)2) under various conditions were studied. In particular, the effects of the transport inhibitors carboxyatractyloside (CATR) and bongkrekic acid (BKA), and fluorescein derivatives were... 

Scheme 1 Solution coupling strategies for DNA conjugation with polymers (a) amide bond formation, (b) formation of disulfide bridges between the thiol groups of both eranponents, and (c) Michael addition of maleimide to ODN fragments functionalized with a snlfhydryl terminal group [11] (figure adapted with permission of Wiley-VCH, Weinheim)...

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