Abstract
This manuscript reviews the possibilities offered by 2,5-dimethylfuran-protected maleimides. Suitably derivatized building blocks incorporating the exo Diels-Alder cycloadduct can be introduced at any position of oligonucleotides, peptide nucleic acids, peptides and peptoids, making use of standard solid-phase procedures. Maleimide deprotection takes place upon heating, which can be followed by either Michael-type or Diels-Alder click conjugation reactions. However, the one-pot procedure in which maleimide deprotection and conjugation are simultaneously carried out provides the target conjugate more quickly and, more importantly, in better yield. This procedure is compatible with conjugates involving oligonucleotides, peptides and peptide nucleic acids. A variety of cyclic peptides and oligonucleotides can be obtained from peptide and oligonucleotide precursors incorporating protected maleimides and thiols.
Highlights
Maleimide-Involving Click Conjugation Reactions with Oligonucleotides and PolyamidesThe Michael-type addition of thiols to electron deficient carbon-carbon double bonds is one of the oldest click reactions [1]
Very recently [14], it has been reported that-oligonucleotides assembled on an alkyl-chain-soluble support can successfully be deprotected by heating in toluene (90 min, 90 °C), and after solvent removal conjugated with a variety of thiol-containing compounds
With the purpose of carrying out two subsequent conjugation reactions in solution, we considered the possibility of exploiting the versatility of maleimide protection to attach maleimides and protected maleimides to a biomolecule
Summary
Maleimide-Involving Click Conjugation Reactions with Oligonucleotides and Polyamides. Very recently [14], it has been reported that (protected maleimido)-oligonucleotides assembled on an alkyl-chain-soluble support can successfully be deprotected by heating in toluene (90 min, 90 °C), and after solvent removal conjugated with a variety of thiol-containing compounds. This methodology, routinely used in our laboratory, has proved successful for others. Both diene- and maleimido-derivatized phosphorothioate oligonucleotides can be reacted with maleimides and thiols, respectively, and provide the target conjugates with no undesired reaction between the thiophosphate diesters and the maleimide
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