Nanomaterial Interfaces in Biology pp 47-73

Part of the Methods in Molecular Biology book series (MIMB, volume 1025) | Cite as

Synthesizing and Modifying Peptides for Chemoselective Ligation and Assembly into Quantum Dot-Peptide Bioconjugates

  • W. Russ Algar
  • Juan B. Blanco-Canosa
  • Rachel L. Manthe
  • Kimihiro Susumu
  • Michael H. Stewart
  • Philip E. Dawson
  • Igor L. Medintz
Protocol

Abstract

Quantum dots (QDs) are well-established as photoluminescent nanoparticle probes for in vitro or in vivo imaging, sensing, and even drug delivery. A critical component of this research is the need to reliably conjugate peptides, proteins, oligonucleotides, and other biomolecules to QDs in a controlled manner. In this chapter, we describe the conjugation of peptides to CdSe/ZnS QDs using a combination of polyhistidine self-assembly and hydrazone ligation. The former is a high-affinity interaction with the inorganic surface of the QD; the latter is a highly efficient and chemoselective reaction that occurs between 4-formylbenzoyl (4FB) and 2-hydrazinonicotinoyl (HYNIC) moieties. Two methods are presented for modifying peptides with these functional groups: (1) solid phase peptide synthesis; and (2) solution phase modification of pre-synthesized, commercial peptides. We further describe the aniline-catalyzed ligation of 4FB- and HYNIC-modified peptides, in the presence of a fluorescent label on the latter peptide, as well as subsequent assembly of the ligated peptide to water-soluble QDs. Many technical elements of these protocols can be extended to labeling peptides with other small molecule reagents. Overall, the bioconjugate chemistry is robust, selective, and modular, thereby potentiating the controlled conjugation of QDs with a diverse array of biomolecules for various applications.

Key words

Quantum dot Peptide Bioconjugation Polyhistidine Self-assembly Chemoselective ligation Hydrazone 

References

  1. 1.
    Algar WR, Prasuhn DE, Stewart MH, Jennings TL, Blanco-Canosa JB, Dawson PE, Medintz IL (2011) The controlled display of biomolecules on nanoparticles: a challenge suited to bioorthogonal chemistry. Bioconjug Chem 22:825–858CrossRefGoogle Scholar
  2. 2.
    Rosi NL, Mirkin CA (2005) Nanostructures in biodiagnostics. Chem Rev 105:1547–1562CrossRefGoogle Scholar
  3. 3.
    Niemeyer CM (2001) Nanoparticles, proteins, and nucleic acids: biotechnology meets materials science. Angew Chem Int Ed 40:4128–4158CrossRefGoogle Scholar
  4. 4.
    Algar WR, Susumu K, Delehanty JB, Medintz IL (2011) Semiconductor quantum dots in bioanalysis: crossing the valley of death. Anal Chem 83:8826–8837CrossRefGoogle Scholar
  5. 5.
    Rosenthal SJ, Chang JC, Kovtun O, McBride JR, Tomlinson ID (2011) Biocompatible quantum dots for biological applications. Chem Biol 18:10–24CrossRefGoogle Scholar
  6. 6.
    Algar WR, Krull UJ (2010) New opportunities in multiplexed bioanalyses using quantum dots and donor-acceptor interactions. Anal Bioanal Chem 398:2439–2449CrossRefGoogle Scholar
  7. 7.
    Bruchez MP (2011) Quantum dots find their stride in single molecule tracking. Curr Opin Chem Biol 15:775–780CrossRefGoogle Scholar
  8. 8.
    Chan WCW, Maxwell DJ, Gao XH, Bailey RE, Han MY, Nie SM (2002) Luminescent quantum dots for multiplexed biological detection and imaging. Curr Opin Biotechnol 13:40–46CrossRefGoogle Scholar
  9. 9.
    Algar WR, Tavares AJ, Krull UJ (2010) Beyond labels: a review of the application of quantum dots as integrated components of assays, bioprobes, and biosensors utilizing optical transduction. Anal Chim Acta 673:1–25CrossRefGoogle Scholar
  10. 10.
    Medintz IL, Mattoussi H (2009) Quantum dot-based resonance energy transfer and its growing application in biology. Phys Chem Chem Phys 11:17–45CrossRefGoogle Scholar
  11. 11.
    Biju V, Itoh T, Anas A, Sujith A, Ishikawa M (2008) Semiconductor quantum dots and metal nanoparticles: syntheses, optical properties, and biological applications. Anal Bioanal Chem 391:2469–2495CrossRefGoogle Scholar
  12. 12.
    Sapsford KE, Pons T, Medintz IL, Higashiya S, Brunel FM, Dawson PE, Mattoussi H (2007) Kinetics of metal-affinity driven self-assembly between proteins or peptides and CdSe-ZnS quantum dots. J Phys Chem C 111:11528–11538CrossRefGoogle Scholar
  13. 13.
    Pons T, Medintz IL, Wang X, English DS, Mattoussi H (2006) Solution-phase single quantum dot fluorescence resonance energy transfer. J Am Chem Soc 128:15324–15331CrossRefGoogle Scholar
  14. 14.
    Prasuhn DE, Blanco-Canosa JB, Vora GJ, Delehanty JB, Susumu K, Mei BC, Dawson PE, Medintz IL (2010) Combining chemoselective ligation with polyhistidine-driven self-assembly for the modular display of biomolecules on quantum dots. ACS Nano 4:267–278CrossRefGoogle Scholar
  15. 15.
    Medintz IL, Berti L, Pons T, Grimes AF, English DS, Alessandrini A, Facci P, Mattoussi H (2007) A reactive peptidic linker for self-assembling hybrid quantum dot-DNA bioconjugates. Nano Lett 7:1741–1748CrossRefGoogle Scholar
  16. 16.
    Blanco-Canosa JB, Medintz IL, Farrell D, Mattoussi H, Dawson PE (2010) Rapid covalent ligation of fluorescent peptides to water solubilized quatnum dots. J Am Chem Soc 132:10027–10033CrossRefGoogle Scholar
  17. 17.
    Dennis AM, Bao G (2008) Quantum dot-fluorescent protein pairs as novel fluorescence resonance energy transfer probes. Nano Lett 8:1439–1445CrossRefGoogle Scholar
  18. 18.
    Zhang Y, So MK, Loening AM, Yao HQ, Gambhir SS, Rao JH (2006) HaloTag protein-mediated site-specific conjugation of bioluminescent proteins to quantum dots. Angew Chem Int Ed 45:4936–4940CrossRefGoogle Scholar
  19. 19.
    Wang JH, Xia J (2011) Preferential binding of a novel polyhistidine peptide dendrimer ligand on quantum dots probed by capillary electrophoresis. Anal Chem 83:6323–6329CrossRefGoogle Scholar
  20. 20.
    Prasuhn DE, Deschamps JR, Susumu K, Stewart MH, Boeneman K, Blanco-Canosa JB, Dawson PE, Medintz IL (2010) Polyvalent display and packing of peptides and proteins on semiconductor quantum dots: predicted versus experimental results. Small 6:555–564CrossRefGoogle Scholar
  21. 21.
    Sawant RM, Hurley JP, Salmaso S, Kale A, Tolcheva E, Levchenko TS, Torchilin VP (2006) “SMART” drug delivery systems: double-targeted pH-responsive pharmaceutical nanocarriers. Bioconjug Chem 17:943–949CrossRefGoogle Scholar
  22. 22.
    Savla R, Taratula O, Garbuzenko O, Minko T (2011) Tumor targeted quantum dot-mucin 1 aptamer-doxorubicin conjugate for imaging and treatment of cancer. J Control Release 153:16–22CrossRefGoogle Scholar
  23. 23.
    Kam NWS, Liu Z, Dai HJ (2005) Functionalization of carbon nanotubes via cleavable disulfide bonds for efficient intracellular delivery of siRNA and potent gene silencing. J Am Chem Soc 127:12492–12493CrossRefGoogle Scholar
  24. 24.
    Takae S, Miyata K, Oba M, Ishii T, Nishiyama N, Itaka K, Yamasaki Y, Koyama H, Kataoka K (2008) PEG-detachable polyplex micelles based on disulfide-linked block catiomers as bioresponsive nonviral gene vectors. J Am Chem Soc 130:6001–6009CrossRefGoogle Scholar
  25. 25.
    Dirksen A, Dawson PE (2008) Rapid oxime and hydrazone ligations with aromatic aldehydes for biomolecular labeling. Bioconjug Chem 19:2543–2548CrossRefGoogle Scholar
  26. 26.
    Chen Y, Aveyard J, Wilson R (2004) Gold and silver nanoparticles functionalized with known numbers of oligonucleotides per particle for DNA detection. Chem Commun 2804–2805Google Scholar
  27. 27.
    Zhong XB, Reynolds R, Kidd JR, Kidd KK, Jenison R, Marlar RA, Ward DC (2003) Single-nucleotide polymorphism genotyping on optical thin-film biosensor chips. Proc Natl Acad Sci USA 100:11559–11564CrossRefGoogle Scholar
  28. 28.
    Chang YS, Jeong JM, Lee YS, Kim HW, Rai GB, Lee SJ, Lee DS, Chung JK, Lee MC (2005) Preparation of F-18-human serum albumin: a simple and efficient protein labeling method with F-18 using a hydrazone-formation method. Bioconjug Chem 16:1329–1333CrossRefGoogle Scholar
  29. 29.
    Steinberg-Tatman G, Huynh M, Barker D, Zhao CF (2006) Synthetic modification of silica beads that allows for sequential attachment of two oligonucleotides. Bioconjug Chem 17:841–848CrossRefGoogle Scholar
  30. 30.
    King PT, Zhao SW, Lam L (1986) Preparation of protein conjugates via intermolecular hydrazone linkage biochemistry. Biochemistry 25:5774–5779CrossRefGoogle Scholar
  31. 31.
    Gaertner HF, Rose K, Cotton R, Timms D, Camble R, Offord RE (1992) Construction of protein analogues by site-specific condensation of unprotected fragments. Bioconjug Chem 3:262–268CrossRefGoogle Scholar
  32. 32.
    Rose K (1994) Facile synthesis of homogeneous artificial proteins. J Am Chem Soc 116:30–33CrossRefGoogle Scholar
  33. 33.
    Weden RC, Lankinen M, Rose K, Blakey D, Shuttleworth H, Melton R, Offord RE (1994) Site-specific conjugation of an enzyme and an antibody fragment. Bioconjug Chem 5:411–417CrossRefGoogle Scholar
  34. 34.
    Canne LE, Ferré-D’Amaré AR, Burley SK, Kent SBH (1995) Total chemical synthesis of a unique transcription factor-related protein: cMyc-Max. J Am Chem Soc 117:2998–3007CrossRefGoogle Scholar
  35. 35.
    Shao J, Tam JP (1995) Unprotected peptides as building blocks for the synthesis of peptide dendrimers with oxime, hydrazone, and thiazolidine linkages. J Am Chem Soc 117:3893–3899CrossRefGoogle Scholar
  36. 36.
    Cervigini SE, Dumy P, Mutter M (1996) Synthesis of glycopeptides and lipopeptides by chemoselective ligation. Angew Chem Int Ed 35:1230–1232CrossRefGoogle Scholar
  37. 37.
    Mahal LK, Yarema KJ, Bertozzi CR (1997) Engineering chemical reactivity on cell surfaces through oligosaccharide biosynthesis. Science 276:1125–1128CrossRefGoogle Scholar
  38. 38.
    Chen I, Howarth M, Lin W, Ting AY (2005) Site-specific labeling of cell surface proteins with biophysical probes using biotin ligase. Nat Methods 2:99–104CrossRefGoogle Scholar
  39. 39.
    Singh Y, Renaudet O, Defrancq E, Dumy P (2005) Preparation of a multitopic glycopeptide-oligonucleotide conjugate. Org Lett 7:1359–1362CrossRefGoogle Scholar
  40. 40.
    Larsen K, Thygesen MB, Guillaumie F, Willats WGT, Jensen K (2006) Solid-phase chemical tools for glycobiology. Carbohydr Res 341:1209–1234CrossRefGoogle Scholar
  41. 41.
    Scheck RA, Francis MB (2007) Regioselective labeling of antibodies through N-terminal transamination. ACS Chem Biol 4:247–251CrossRefGoogle Scholar
  42. 42.
    Carrico IS, Carlson LB, Bertozzi CR (2007) Introducing genetically encoded aldehydes into proteins. Nat Chem Biol 3:321–322CrossRefGoogle Scholar
  43. 43.
    Dirksen A, Dirksen S, Hackeng TM, Dawson PE (2006) Nucleophilic catalysis of hydrazone formation and transamination: implications for dynamic covalent chemistry. J Am Chem Soc 128:15602–15603CrossRefGoogle Scholar
  44. 44.
    Dirksen A, Hackeng TM, Dawson PE (2006) Nucleophilic catalysis of oxime ligation. Angew Chem Int Ed 118:7743–7746CrossRefGoogle Scholar
  45. 45.
    Sarin VK, Kent SB, Tam JP, Merrifield RB (1981) Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction. Anal Biochem 117:147–157CrossRefGoogle Scholar
  46. 46.
    Dabbousi BO, Rodriguez-Viejo J, Mikulec FV, Heine JR, Mattoussi H, Ober R, Jensen KF, Bawendi MG (1997) (CdSe)ZnS core-shell quantum dots: synthesis and optical and structural characterization of a size series of highly luminescent materials. J Phys Chem B 101:9463–9475CrossRefGoogle Scholar
  47. 47.
    Susumu K, Oh E, Delehanty JB, Blanco-Canosa JB, Johnson BJ, Jain V, Hervey WJ, Algar WR, Boeneman K, Dawson PE, Medintz IL (2011) Multifunctional compact zwitterionic ligands for preparing robust biocompatible semiconductor quatnum dots and gold nanoparticles. J Am Chem Soc 133:9480–9496CrossRefGoogle Scholar
  48. 48.
    Mei BC, Susumu K, Medintz IL, Mattoussi H (2009) Polyethylene glycol-based bidentate ligands to enhance quantum dot and gold nanoparticle stability in biological media. Nat Protoc 4:412–423CrossRefGoogle Scholar
  49. 49.
    Surfraz MBU, King R, Mather SJ, Biagini SCG, Blower PJ (2007) Trifluoroacetyl-HYNIC peptides: synthesis and 99mTc radiolabeling. J Med Chem 50:1418–1422CrossRefGoogle Scholar
  50. 50.
    Dennis AM, Sotto DC, Mei BC, Medintz IL, Mattoussi H, Bao G (2010) Surface ligand effects on metal-affinity coordination to quantum dots: implications for nanoprobe self-assembly. Bioconjug Chem 21:1160–1170CrossRefGoogle Scholar
  51. 51.
    Prasuhn DE, Susumu K, Medintz IL (2011) Multivalent conjugation of peptides, proteins, and DNA to semiconductor quantum dots. In: Hurst SJ (ed) Biomedical nanotechnology: methods and protocols. Humana Press-Springer, New York, pp 95–110CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • W. Russ Algar
    • 1
  • Juan B. Blanco-Canosa
    • 2
  • Rachel L. Manthe
    • 3
  • Kimihiro Susumu
    • 1
  • Michael H. Stewart
    • 4
  • Philip E. Dawson
    • 2
  • Igor L. Medintz
    • 5
  1. 1.Naval Research LaboratoryWashington, DCUSA
  2. 2.Scripps Research InstituteLa JollaUSA
  3. 3.Sotera Defense SolutionsUniversity of MarylandCollege ParkUSA
  4. 4.Division of Optical SciencesU.S. Naval Research LaboratoryWashington, DCUSA
  5. 5.U.S. Naval Research LaboratoryCenter for Bio/Molecular Science and EngineeringWashington, DCUSA

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