Improved peptidyl linkers for self-assembly of semiconductor quantum dot bioconjugates

Lorenzo Berti, Paola Serena D'Agostino, Kelly Boeneman, Igor L. Medintz

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

We demonstrate improved peptide linkers which allow both conjugation to biomolecules such as DNA and self-assembly with luminescent semiconductor quantum dots. A hexahistidine peptidyl sequence was generated by standard solid phase peptide synthesis and modified with the succinimidyl ester of iodoacetamide to yield a thiol-reactive iodoacetyl polyhistidine linker. The reactive peptide was conjugated to dye-labeled thiolated DNA which was utilized as a model target biomolecule. Agarose gel electrophoresis and fluorescence resonance energy transfer analysis confirmed that the linker allowed the DNA to self-assemble with quantum dots via metal-affinity driven coordination. In contrast to previous peptidyl linkers that were based on disulfide exchange and were thus labile to reduction, the reactive haloacetyl chemistry demonstrated here results in a more stable thioether bond linking the DNA to the peptide which can withstand strongly reducing environments such as the intracellular cytoplasm. As thiol groups occur naturally in proteins, can be engineered into cloned proteins, inserted into nascent peptides or added to DNA during synthesis, the chemistry demonstrated here can provide a simple method for self-assembling a variety of stable quantum dot bioconjugates.

Original languageEnglish (US)
Pages (from-to)121-129
Number of pages9
JournalNano Research
Volume2
Issue number2
DOIs
StatePublished - 2009

Keywords

  • Bioconjugation
  • DNA
  • Fluorescence
  • Fluorescence resonance energy transfer (FRET)
  • Iodoacetyl
  • Metal-affinity
  • Nanocrystal
  • Peptide
  • Polyhistidine
  • Semiconductor quantum dot
  • Sulfhydryl

ASJC Scopus subject areas

  • Electrical and Electronic Engineering
  • Materials Science(all)

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