A new water soluble 3,6,9-trioxaundecanedioic acid-based linker and biotinylating reagent

Biotinylated peptides often have low solubility in water. In this Letter, we describe a new method to synthesize a biotinylating reagent for water-solubilizing hydrophobic peptides. The biotinyl-6-aminohexanoic derivatives prepared contain a hydrophilic 3,6,9-trioxaundecanedioic acid linker moiety between the biotin and the peptide to improve the water solubility, and also to function as a spacer. The monoesterified derivative of 3,6,9-trioxaundecanedioic acid was synthesized, and the Fmoc-protected ethylenediamine was used to link to the carboxylic group of biotin. The hydrophilic nature of this new biotin–peptide conjugate was also demonstrated in a comparative analysis of compounds containing a biotinyl-6-aminohexanoic acid or 3,6,9-trioxaundecanedioic acid derivative.