A novel heterotrifunctional peptide-based cross-linking reagent for facile access to bioconjugates. Applications to peptide fluorescent labelling and immobilisation

Org Biomol Chem. 2008 Sep 7;6(17):3065-78. doi: 10.1039/b807263a. Epub 2008 Jun 30.

Abstract

A convenient, versatile and straightforward synthesis of a novel heterotrifunctional peptide-based linker molecule is described. This generic bio-labelling reagent contains an amine-reactive N-hydroxysuccinimidyl carbamate moiety, an aldehyde/ketone-reactive aminooxy group and a thiol group with a propensity to form urea, oxime and thioether linkages respectively. The full chemical orthogonality between the free aminooxy and thiol functionalities was demonstrated through the preparation of a fluorescent reagent suitable for the selective staining of a carboxaldehyde-modified surface by means of oxime ligation. The absence of reactivity of these two functions toward the nucleophile-sensitive active carbamate was obtained by using temporary aminooxy- and thiol-protecting groups removable under mild conditions. The utility of the linker molecule to cross-link three different molecular partners has been illustrated by the preparation of fluorescent tripod-functionalised surfaces which may be useful in developing new peptide microarrays and related immunosensors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cross-Linking Reagents / chemical synthesis*
  • Cross-Linking Reagents / chemistry
  • Fluorescence Resonance Energy Transfer
  • Fluorescent Dyes / chemistry*
  • Fluoroimmunoassay / methods*
  • Substance P / chemistry*
  • Substance P / immunology
  • Substance P / metabolism*
  • Sulfhydryl Compounds / chemistry

Substances

  • Cross-Linking Reagents
  • Fluorescent Dyes
  • Sulfhydryl Compounds
  • Substance P