Attachment of Peptide Building Blocks to Proteins Through Tyrosine Bioconjugation

Dante W. Romanini† and Matthew B. Francis*‡
Department of Chemistry, University of California, Berkeley, California 94720-1460, and Materials Sciences Division, Lawrence Berkeley National Labs, Berkeley, California 94720-1460
Bioconjugate Chem., 2008, 19 (1), pp 153–157
DOI: 10.1021/bc700231v
Publication Date (Web): December 11, 2007
Copyright © 2008 American Chemical Society
†

University of California.

,
* Corresponding author. Phone: 510-643-9915 . Fax: 510-643-3079. E-mail: francis@cchem.berkeley.edu.
,
‡

Lawrence Berkeley National Labs.

Abstract

Recent efforts have yielded a number of short peptide sequences with useful binding, sensing, and cellular uptake properties. In order to attach these sequences to tyrosine residues on intact proteins, a three-component Mannich-type strategy is reported. Two solid phase synthetic routes were developed to access peptides up to 20 residues in length with anilines at either the N- or C-termini. In the presence of 20 mM formaldehyde, these functional groups were coupled to tyrosine residues on proteins under mild reaction conditions. The identities of the resulting bioconjugates were confirmed using mass spectrometry and immunoblot analysis. Screening experiments have demonstrated that the method is compatible with substrates containing all of the amino acids, including lysine and cysteine residues. Importantly, tyrosine residues on proteins exhibit much faster reaction rates, allowing short peptides containing this residue to be coupled without cross reactions.

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History

  • Published In Issue January 16, 2008
  • Article ASAPDecember 11, 2007
  • Received: June 21, 2007
    Revised: October 04, 2007

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