Skip to main content

Application of Fluorescence in Studying Therapeutic Enzymes

  • Chapter
  • First Online:
Therapeutic Enzymes: Function and Clinical Implications

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1148))

Abstract

Fluorescence spectroscopy is one of the most important techniques in the study of therapeutic enzymes. The fluorescence phenomenon has been discovered and exploited for centuries, while therapeutic enzymes have been used in treatment of disease for only decades. This chapter provides a brief summary of the current applications of fluorescence methods in studying therapeutic enzymes to provide some insights on the selection of proper method tailored to the goal. First a brief introduction about therapeutic enzymes and history of fluorescence were provided, followed by discussions on how fluorescence was applied in the studies. Four popular fluorescence methods are discussed: fluorescence tracing, fluorescence resonance energy transfer (FRET), fluorescence quenching and fluorescence polarization. Selected application of the fluorescence methods in studying therapeutic enzymes are listed, and discussed in details in the following paragraphs.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

FRET:

Fluorescence resonance energy transfer

MS:

Mass spectroscopy

CD:

Circular dichroism

FTIR:

Fourier-transform infrared spectroscopy

US-FDA:

Food and Drug Administration in USA

SCID:

Severe combined immunodeficiency disease

mAbs:

Monoclonal antibodies

IgG1:

Immunoglobulin G1

GFP:

Green Fluorescent Protein

GBA:

Glucocerebrosidase

ABP:

Activity-based probes

MCL:

Mantle cell lymphoma

MESK:

Microencapsulated streptokinase

FREE SK:

Unencapsulated streptokinase

CFP:

Cyan fluorescent protein

YFP:

Yellow fluorescent protein

Abl:

Ableson

Bcr:

Break point cluster

ECFP:

Enhanced cyan fluorescent protein

HPMA:

N-(2-hydroxypropyl) methacrylamide

ADA:

Adenosine deaminase

FAM:

6-carboxyfluo rescein

MWCNTs:

Multi-walled carbon nanotubes

IgE:

Immunoglobulin E

FcεRI:

The IgE Fc receptor

IFN-γ:

Interferon gamma

References

  • Alinari L, Yu B, Christian BA et al (2011) Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma. Blood 117(17):4530–4541

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • American Diabetes A (2010) Diagnosis and classification of diabetes mellitus. Diabetes Care 33(Suppl 1):S62–S69

    Article  Google Scholar 

  • Carter PJ, Lazar GA (2018) Next generation antibody drugs: pursuit of the ‘high-hanging fruit’. Nat Rev Drug Discov 17(3):197–223

    Article  CAS  PubMed  Google Scholar 

  • Chan AC, Carter PJ (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10:301

    Article  CAS  PubMed  Google Scholar 

  • Ciftci HI, Ozturk SE, Ali TFS et al (2018) The first pentacyclic triterpenoid gypsogenin derivative exhibiting anti-ABL1 kinase and anti-chronic myelogenous leukemia activities. Biol Pharm Bull 41(4):570–574

    Article  CAS  PubMed  Google Scholar 

  • Falach A, Nathan I, Baram S et al (1997) Interaction of a novel fluorescent analog of interferon-γ with transformed cells. Bioconjug Chem 8(4):459–465

    Article  CAS  PubMed  Google Scholar 

  • Goldberg DM (1992) Enzymes as agents for the treatment of disease. Clin Chim Acta 206(1):45–76

    Article  CAS  PubMed  Google Scholar 

  • Helms V (2008) Principles of computational cell biology: from protein complexes to cellular networks. Wiley, Weinheim, pp 39–59

    Google Scholar 

  • Hodi FS, O’Day SJ, McDermott DF et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu K, Huang Y, Wang S et al (2014) A carbon nanotubes based fluorescent aptasensor for highly sensitive detection of adenosine deaminase activity and inhibitor screening in natural extracts. J Pharm Biomed Anal 95:164–168

    Article  CAS  PubMed  Google Scholar 

  • Jones SA, Shim SH, He J et al (2011) Fast, three-dimensional super-resolution imaging of live cells. Nat Methods 8(6):499–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kallemeijn WW, Scheij S, Hoogendoorn S et al (2017) Investigations on therapeutic glucocerebrosidases through paired detection with fluorescent activity-based probes. PLoS One 12(2):e0170268

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kim B, Eggel A, Tarchevskaya SS et al (2012) Accelerated disassembly of IgE-receptor complexes by a disruptive macromolecular inhibitor. Nature 491:613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinch MS (2015) An overview of FDA-approved biologics medicines. Drug Discov Today 20(4):393–398

    Article  CAS  PubMed  Google Scholar 

  • Kurokawa K, Mochizuki N, Ohba Y et al (2001) A pair of fluorescent resonance energy transfer-based probes for tyrosine phosphorylation of the CrkII adaptor protein in vivo. J Biol Chem 276(33):31305–31310

    Article  CAS  PubMed  Google Scholar 

  • Leach JK, Patterson E, O’Rear EA (2004) Distributed intraclot thrombolysis: mechanism of accelerated thrombolysis with encapsulated plasminogen activators. J Thromb Haemost 2(9):1548–1555

    Article  CAS  PubMed  Google Scholar 

  • Leader B, Baca QJ, Golan DE (2008) Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov 7:21

    Article  CAS  PubMed  Google Scholar 

  • Li M, Liu L, Xi N et al (2011) Imaging and measuring the rituximab-induced changes of mechanical properties in B-lymphoma cells using atomic force microscopy. Biochem Biophys Res Commun 404(2):689–694

    Article  CAS  PubMed  Google Scholar 

  • Li S, Yang X, Yang S et al (2012) Technology prospecting on enzymes: application, marketing and engineering. Comput Struct Biotechnol J 2:e201209017

    Article  PubMed  PubMed Central  Google Scholar 

  • Manchester KL (1995) Louis Pasteur (1822–1895) – chance and the prepared mind. Trends Biotechnol 13(12):511–515

    Article  CAS  PubMed  Google Scholar 

  • McLaughlin P, Grillo-López AJ, Link BK et al (1998) Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 16(8):2825–2833

    Article  CAS  PubMed  Google Scholar 

  • Miyawaki A, Llopis J, Heim R et al (1997) Fluorescent indicators for Ca2+based on green fluorescent proteins and calmodulin. Nature 388:882–887

    Article  CAS  PubMed  Google Scholar 

  • Murai T, Kawashima H (2008) A simple assay for hyaluronidase activity using fluorescence polarization. Biochem Biophys Res Commun 376(3):620–624

    Article  CAS  PubMed  Google Scholar 

  • Nath CE, Dallapozza L, Eslick AE (2008) An isocratic fluorescence HPLC assay for the monitoring of l-asparaginase activity and l-asparagine depletion in children receiving E. coli l-asparaginase for the treatment of acute lymphoblastic leukaemia. Biomed Chromatogr 23(2):152–159

    Article  CAS  Google Scholar 

  • Nowell PC (2007) Discovery of the Philadelphia chromosome: a personal perspective. J Clin Invest 117(8):2033–2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Piepenhagen PA, Vanpatten S, Hughes H (2010) Use of direct fluorescence labeling and confocal microscopy to determine the biodistribution of two protein therapeutics, Cerezyme® and Ceredase®. Microsc Res Tech 73(7):694–703

    CAS  PubMed  Google Scholar 

  • Pietraszewska-Bogiel A, Gadella TW (2011) FRET microscopy: from principle to routine technology in cell biology. J Microsc 241(2):111–118

    Article  CAS  PubMed  Google Scholar 

  • Piston DW, Kremers GJ (2007) Fluorescent protein FRET: the good, the bad and the ugly. Trends Biochem Sci 32(9):407–414

    Article  CAS  PubMed  Google Scholar 

  • Schulz JD, Patt M, Basler S et al (2016) Site-specific polymer conjugation stabilizes therapeutic enzymes in the gastrointestinal tract. Adv Mater 28(7):1455–1460

    Article  CAS  PubMed  Google Scholar 

  • Shahzad A, Köhler G, Knapp M et al (2009) Emerging applications of fluorescence spectroscopy in medical microbiology field. J Transl Med 7:99

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shaner NC, Campbell RE, Steinbach PA et al (2004) Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein. Nat Biotechnol 22:1567–1572

    Article  CAS  PubMed  Google Scholar 

  • Shaner NC, Steinbach PA, Tsien RY (2005) A guide to choosing fluorescent proteins. Nat Methods 2:905–909

    Article  CAS  PubMed  Google Scholar 

  • Szittner Z, Papp K, Sándor N et al (2013) Application of fluorescent monocytes for probing immune complexes on antigen microarrays. PLoS One 8(9):e72401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tatford OC, Gomme PT, Bertolini J (2004) Analytical techniques for the evaluation of liquid protein therapeutics. Biotechnol Appl Biochem 40(1):67–81

    Article  CAS  PubMed  Google Scholar 

  • Tompa P, Batke J, Ovadi J et al (1987) Quantitation of the interaction between citrate synthase and malate dehydrogenase. J Biol Chem 262(13):6089–6092

    Article  CAS  PubMed  Google Scholar 

  • Tunceroglu A, Matsuda M, Birge RB (2010) Real-time fluorescent resonance energy transfer analysis to monitor drug resistance in chronic myelogenous leukemia. Mol Cancer Ther 9(11):3065–3073

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tyagarajan K, Pretzer E, Wiktorowicz JE (2003) Thiol-reactive dyes for fluorescence labeling of proteomic samples. Electrophoresis 24(14):2348–2358

    Article  CAS  PubMed  Google Scholar 

  • Usmani SS, Bedi G, Samuel JS et al (2017) THPdb: database of FDA-approved peptide and protein therapeutics. PLoS One 12(7):e0181748

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Valeur B, Berberan-Santos MN (2011) A brief history of fluorescence and phosphorescence before the emergence of quantum theory. J Chem Educ 88(6):731–738

    Article  CAS  Google Scholar 

  • Vellard M (2003) The enzyme as drug: application of enzymes as pharmaceuticals. Curr Opin Biotechnol 14(4):444–450

    Article  CAS  PubMed  Google Scholar 

  • Verhamme IM, Bock PE (2014) Rapid binding of plasminogen to streptokinase in a catalytic complex reveals a three-step mechanism. J Biol Chem 289(40):28006–28018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wakabayashi H, Fay PJ (2013) Molecular orientation of factor VIIIa on the phospholipid membrane surface determined by fluorescence resonance energy transfer. Biochem J 452(2):293–301

    Article  CAS  PubMed  Google Scholar 

  • Wei H, Mo J, Tao L et al (2014) Hydrogen/deuterium exchange mass spectrometry for probing higher order structure of protein therapeutics: methodology and applications. Drug Discov Today 19(1):95–102

    Article  CAS  PubMed  Google Scholar 

  • Yadav AK, Shen DL, Shan X et al (2015) Fluorescence-quenched substrates for live cell imaging of human glucocerebrosidase activity. J Am Chem Soc 137(3):1181–1189

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Luo K, Pan H et al (2011) Synthesis of biodegradable multiblock copolymers by click coupling of RAFT-generated HeterotelechelicPolyHPMA conjugates. React Funct Polym 71(3):294–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye C, Wang Z, Lu W et al (2014) Unfolding study of a trimeric membrane protein AcrB. Protein Sci 23(7):897–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi NY, He Q, Caligan TB et al (2015) Development of a cell-based fluorescence polarization biosensor using preproinsulin to identify compounds that alter insulin granule dynamics. Assay Drug Dev Technol 13(9):558–569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan T, Weljie AM, Vogel HJ (1998) Tryptophan fluorescence quenching by methionine and selenomethionine residues of calmodulin: orientation of peptide and protein binding. Biochemistry 37(9):3187–3195

    Article  CAS  PubMed  Google Scholar 

  • Zhang R, Yang J, Radford DC et al (2017) FRET imaging of enzyme-responsive HPMA copolymer conjugate. Macromol Biosci 17(1):1600125

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zhaoshuai Wang .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wang, Z., Li, C., Wei, Y. (2019). Application of Fluorescence in Studying Therapeutic Enzymes. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_5

Download citation

Publish with us

Policies and ethics