Periplasmic Binding Proteins in Biosensing Applications

  • Felix S. Grünewald
Part of the Bioanalytical Reviews book series (BIOREV, volume 1)


Periplasmic binding proteins (PBPs) of gram-negative bacteria have been widely used as recognition elements for the development of biosensors for small molecule analytes owing to their intrinsically high selectivity and affinity towards their cognate ligands. Analyte binding is accompanied by a large hinge motion that can readily be transduced to a detectable signal. While fundamental work demonstrating the versatility of PBPs as scaffolds for biosensors dates back to the 1990s, recent years have seen more subtle improvements in detection strategies. Measurement of cellular metabolites with PBP-based biosensors has allowed significant contributions to basic research, and a first functional sensor for continuous blood glucose monitoring with glucose-binding protein as biological recognition element was tested in preclinical trials. In this chapter, strategies and applications of biosensors using PBPs as specifiers will be reviewed.


Periplasmic binding proteins Affinity based biosensors Solvatochromism Fluorescence biosensors 



Ruthenium tris(2,2′-bipyridine)dichloride




Allose-binding protein




Alexa Fluor 488


Alexa Fluor 680


Alexa Fluor 750


2-(4′-Iodoacetamidoanilino)naphtalene-6-sulphonic acid






Binding protein


Bioluminescence resonance energy transfer


Circularly permuted GFP


Enhanced cyan fluorescent protein




Enhanced yellow fluorescent protein


Fluorescent indicator proteins


Fluorescent protein


Förster resonance energy transfer


Glucose-/galactose-binding protein


Green fluorescent protein


Glutamine-binding protein


5-(Iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid




Dissociation constant


Branched-chain (leucine, isoleucine, valine) amino acid-binding protein


Maltose-binding protein








Nickel nitrilotriacetic acid


Near infrared


Nuclear magnetic resonance


Periplasmic binding protein


Polyethylene glycol


PEG-dimethacrylate/methacrylic acid copolymer


Paramagnetic resonance enhancement


Protein Data Bank


Ribose-binding protein


Rhodamine red




Squarewave voltammetry


Tetramethyl rhodamine


Fluorescence intensity change


Fluorescence lifetime



I would like to thank Stacy DuVall for helpful discussions on electrochemical topics and critical reading of the draft. Thomas Meier is acknowledged for valuable suggestions to the draft. This work was promoted by the European Union under grant agreement number 264772 (ITN CHEBANA).


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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Felix S. Grünewald
    • 1
    • 2
  1. 1.Department of Chemistry DevelopmentRoche Diabetes Care, Roche Diagnostics GmbHMannheimGermany
  2. 2.Department of Biotechnology DevelopmentRoche Professional Diagnostics, Roche Diagnostics GmbHPenzbergGermany

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