Research Article


2009, 2: 121-129


Improved Peptidyl Linkers for Self-Assembly of Semiconductor Quantum Dot Bioconjugates

Lorenzo Berti 1,2, Paola Serena D’Agostino1 , Kelly Boeneman3 , and Igor L. Medintz3()

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1CNR-INFM, National Research Center on nanoStructures and bioSystems at Surfaces (S3), Via Campi, 213/A 41100 Modena, Italy
2University of California Davis Medical Center, Sacramento, CA 95817, USA
3Center for Bio/Molecular Science and Engineering Code 6900, U.S. Naval Research Laboratory, Washington, DC 20375, USA

Keywords: Semiconductor quantum dot, peptide, DNA, nanocrystal, bioconjugation, iodoacetyl, sulfhydryl, polyhistidine, metal-af? nity, ? uorescence, ? uorescence resonance energy transfer (FRET)
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  • Abstract
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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 ? uorescence resonance energy transfer analysis con? rmed that the linker allowed the DNA to self-assemble with quantum dots via metal-af? nity driven coordination. In contrast to previous peptidyl linkers that were based on disul? de 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.
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Improved Peptidyl Linkers for Self-Assembly of Semiconductor Quantum Dot Bioconjugates. Nano Res. 2009, 2: 121-129

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