Brain Structure and Function

, Volume 217, Issue 3, pp 687–718 | Cite as

Brainpeps: the blood–brain barrier peptide database

  • Sylvia Van Dorpe
  • Antoon Bronselaer
  • Joachim Nielandt
  • Sofie Stalmans
  • Evelien Wynendaele
  • Kurt Audenaert
  • Christophe Van De Wiele
  • Christian Burvenich
  • Kathelijne Peremans
  • Hung Hsuchou
  • Guy De Tré
  • Bart De Spiegeleer


Peptides are able to cross the blood–brain barrier (BBB) through various mechanisms, opening new diagnostic and therapeutic avenues. However, their BBB transport data are scattered in the literature over different disciplines, using different methodologies reporting different influx or efflux aspects. Therefore, a comprehensive BBB peptide database (Brainpeps) was constructed to collect the BBB data available in the literature. Brainpeps currently contains BBB transport information with positive as well as negative results. The database is a useful tool to prioritize peptide choices for evaluating different BBB responses or studying quantitative structure–property (BBB behaviour) relationships of peptides. Because a multitude of methods have been used to assess the BBB behaviour of compounds, we classified these methods and their responses. Moreover, the relationships between the different BBB transport methods have been clarified and visualized.


Peptides Blood–brain barrier Permeability Distribution Brainpeps database 

List of symbols


Percentage injected dose


Surface tension


Surface tension in pure buffer solution


Dielectric constant


Terminal rate constant


Surface pressure


Surface excess concentration


Limited surface excess concentration


Area of the filter, membrane surface area, capillary surface area

ABC transporter

ATP-binding cassette transporter


Surface area of the test compound at the air–water interface


Amount of test compound in brain


Cross-sectional area; surface area


Adenosine triphosphate


Area under the concentration curve


Area under the concentration curve in brain


Area under the concentration curve in plasma


Brain-to-plasma concentration ratio at steady-state, blood–brain equilibrium distribution


Blood–brain barrier


Blood–brain barrier permeability index


Breast cancer resistance protein


Blood–cerebrospinal fluid barrier


Brain efflux index


Brain microvessel endothelial cells


Brain-to-plasma concentration ratio at steady-state, blood–brain equilibrium distribution


Blood–brain barrier peptide database


Bovine serum albumin


Brain uptake index


Body weight


Concentration of test compound


Initial concentration in donor chamber; minimum concentration to induce surface activity

Ca, CA, Cacc

Apical (luminal) side concentration, i.e. in the acceptor chamber


Human colon carcinoma cell line


Calcein acetoxymethyl ester


Cerebral blood flow

Cbr, Cbrain

Brain concentration

Cbr,tot, Cbr (total)

Total brain concentration


Concentration in buffer


Concentration in the CSF


Compartmental distribution

Cdonor, Cd, CD, CDO, CI

Initial concentration of test compound in donor chamber


Concentration of the dialysate


Concentration of test compound in brain ECF


Concentration of the perfusate; concentration in the carotid injection solution


Concentration of intravascular marker




Efflux clearance


Hepatic clearance


Uptake clearance


Systemic clearance


Renal clearance


Systemic clearance


Clearance of the test experiment


Initial uptake clearance


Critical micelle concentration


Central nervous system


Low brain penetrator


High brain penetrator


Concentration ratio of test and reference compound in brain


Concentration ratio of test and reference compound in injection solution


Concentration test compound in organic phase

Cout, Cdial

Concentration of the dialysate

Cp (t)

Plasma concentration at time t


Arterial plasma concentration

Cperfusion, Cperf

Concentration in the perfusion solution


Plasma concentration


Total plasma concentration


Concentration of the reference compound


Concentration of the reference compound in the brain


Concentration of the reference compound in the injected solutions


Concentration of the sample


Saturated concentration at which the surface pressure collapses


Cerebrospinal fluid


Free drug concentration in tissue slice


Concentration of the test compound


Concentration of the test compound in the brain


Concentration of the test compound in the injected solutions


Tissue concentration of the indicator


Total concentration


Unbound concentration


Unbound concentration in brain


Unbound concentration in plasma


Concentration test compound in aqueous phase


Concentration of ionic species of test compound in aqueous phase


Concentration of neutral species of test compound in aqueous phase


Distribution coefficient; dilution factor


Transport rate of test compound


Extraction of the test compound


Extracellular fluid


Dose producing 50% of the maximum response


Ethylenediaminetetraacetic acid


Efflux ratio; entity-relationship


Single pass extraction of the reference compound


Extraction of the permeable marker


Extraction of the vascular impermeable marker


Single pass extraction of the test compound


Exposure time


Regional flow rate


Fraction of plasma exchangeable compound


Foreign key


Unbound fraction


Unbound fraction in brain


Diluted unbound fraction


Free fraction measured


Unbound fraction in plasma


Glomerular filtration rate


Glucose transporter 1


Human α1 acid glycoprotein


High-performance liquid chromatography


Immobilized artificial membrane


International Union of Pure and Applied Chemistry


Brain uptake rate


Maximal flux


Air–water partition coefficient


Dissociation constant


Apparent efflux rate constant


Plasma elimination rate constant


Efflux rate constant


Unidirectional influx rate constant determined with imaging techniques


IAM capacity factor


Unidirectional influx rate constant


Michaelis–Menten constant


Brain elimination rate constant


Brain-to-plasma partition coefficient


Apparent brain-to-plasma partition coefficient


Brain-to-plasma concentration ratio


Intrinsic plasma-to-brain partition coefficient


Brain-to-plasma partition coefficient of the free compound concentration


Large neutral amino acid transporter-1

Log Pcyclohexane/water

Log P value of the cyclohexane/water system

Log Poct/water

Log P value of the 1-octanol/water system


Mouse brain uptake assay


Monocarboxylic transporters


Madin–Darby canine kidney cells


Multidrug resistance gene


Method identification


Magnetic resonance imaging


Multidrug resistance associated protein-1


Avogadro constant


Radioactivity measured per volume serum


Radioactivity measured per gram tissue


Origin identification


Partition coefficient; permeability coefficient


Parallel artificial membrane permeation assay


Apparent permeability coefficient, determined with BMEC, co-culture, immortalized cell lines, Caco-2, MDCK and MBUA

Papp (AB)

Apparent permeability coefficient from apical to basolateral side

Papp (B–A)

Apparent permeability coefficient from basolateral to apical side


Apparent permeability coefficient, determined with PAMPA


Brain parietal cortex area 2


Publication identification


Intrinsic carrier-mediated permeability

\( P_{\text{c}}^{\prime } \)

Apparent net carrier-mediated permeability


Endothelial permeability, effective PAMPA permeability


Effective PAMPA permeability


Endothelial permeability coefficient, determined with BMEC culture


Peptide transporter 1


Positron emission tomography


Permeability of the filter




Permeability index


Peptide IDentification


Monolayer permeability determined with BMEC


Passive diffusive permeability


Peak response


Permeability–surface area coefficient


PS product for the endothelial cell monolayer


PS product of the control filter


Total PS product


Total permeability


Cerebral blood flow

\( \dot{Q} \)

Rate of blood flow


Quantitative autoradiography


Gas constant; recovery


In vitro efflux rate


Immortalized primary rat brain endothelial cells


Recovery by gain


Response identification


Recovery by loss, retrodialysis


Reversed-phase HPLC


Relative recovery


Capillary surface area


Simplified molecular input line entry specification


Single photon emission tomography


Simian vacuolating virus 40


Temperature; perfusion time




Dead time


(Terminal) half-life


Equilibration half-life


Intrinsic equilibration half-life


Perfusion time


Transendothelial electrical resistance


Transfected mouse endothelial cells


Retention time of test compound


Transfected rat endothelial cells


Unified modelling language


Initial distribution volume; plasma distribution volume of marker

Vacc, VA

Volume of the acceptor compartment

Vbr, Vb

Distribution volume in brain


Volume of donor compartment; distribution volume in brain


Volume fraction of brain


Initial distribution volume; Volume of buffer film remaining around sample slice


Maximum uptake rate


Plasma distribution volume


Volume of acceptor compartment


Unbound brain distribution volume


Brain vascular volume


Amount of test compound in acceptor compartment



This work was supported by a PhD grant of ‘Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)’ (73402 to S.V.D.).


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Sylvia Van Dorpe
    • 1
  • Antoon Bronselaer
    • 2
  • Joachim Nielandt
    • 2
  • Sofie Stalmans
    • 1
  • Evelien Wynendaele
    • 1
  • Kurt Audenaert
    • 3
  • Christophe Van De Wiele
    • 4
  • Christian Burvenich
    • 5
  • Kathelijne Peremans
    • 5
  • Hung Hsuchou
    • 6
  • Guy De Tré
    • 2
  • Bart De Spiegeleer
    • 1
  1. 1.Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical SciencesGhent UniversityGhentBelgium
  2. 2.Department of Telecommunications and Information Processing, Faculty of Engineering and ArchitectureGhent UniversityGhentBelgium
  3. 3.Department of Psychiatry and Medical Psychology, Faculty of Medicine and Health SciencesGhent Hospital UniversityGhentBelgium
  4. 4.Department of Radiotherapy and Nuclear Medicine, Faculty of Medicine and Health SciencesGhent Hospital UniversityGhentBelgium
  5. 5.Departments of Physiology and Medical Imaging, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
  6. 6.Pennington Biomedical Research Center, BBB GroupBaton RougeUSA

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