Project

Back to overview

Cell-penetrating peptides, protein folding and multi-drug resistance

English title Cell-penetrating peptides, protein folding and multi-drug resistance
Applicant Huwyler Jörg
Number 129701
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Biophysikalische Chemie Biozentrum der Universität Basel
Institution of higher education University of Basel - BS
Main discipline Biophysics
Start/End 01.06.2010 - 31.05.2013
Approved amount 358'000.00
Show all

Keywords (10)

cell penetrating peptides; CPP; Alzheimer peptide; isothermal titration calorimetry; membrane-induced peptide folding; lipid membranes; P-glycoprotein; blood brain barrier; membrane transport;

Lay Summary (English)

Lead
Lay summary
The group of J. Seelig is interested in cell penetrating peptides which are potential candidates for drug transport. In a related study they investigate the aggregation of Alzheimer peptides on the surface of biological membranes. The group of A. Seelig is interested in the quantitative analysis of multi-drug resistance. They investigate the physico-chemical and mechanistic aspects of trans-membrane proteins such as P-glycoprotein which act as "vacuum cleaners" for toxic substances.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein
Perspicace S, Rufer AC, Thoma R, Mueller F, Hennig M, Ceccarelli S, Schulz-Gasch T, Seelig J (2013), Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein, in FEBS Open Bio, 3, 204-211.
Sav1866 from Staphylococcus aureus and P-Glycoprotein: Similarities and Differences in ATPase Activity Assessed with Detergents as Allocrites.
Beck Andreas, Aänismaa Päivi, Li-Blatter Xiaochun, Dawson Roger, Locher Kaspar, Seelig Anna (2013), Sav1866 from Staphylococcus aureus and P-Glycoprotein: Similarities and Differences in ATPase Activity Assessed with Detergents as Allocrites., in Biochemistry, 52(19), 3297-3309.
The Brain Entry of HIV-1 Protease Inhibitors Is Facilitated When Used in Combination.
Marzolini Catia, Mueller Rita, Li-Blatter Xiaochun, Battegay Manuel, Seelig Anna (2013), The Brain Entry of HIV-1 Protease Inhibitors Is Facilitated When Used in Combination., in Molecular pharmaceutics, ahead of p.
Interaction of the antimicrobial peptide gomesin with model membranes
Domingues T., Mattei B., Seelig J., Perez K. R., Riske K. A., Miranda A. (2012), Interaction of the antimicrobial peptide gomesin with model membranes, in JOURNAL OF PEPTIDE SCIENCE, 18, 63-63.
P-Glycoprotein-ATPase Modulation: The Molecular Mechanisms
Li-Blatter Xiaochun, Beck Andreas, Seelig Anna (2012), P-Glycoprotein-ATPase Modulation: The Molecular Mechanisms, in BIOPHYSICAL JOURNAL, 102(6), 1383-1393.
The Anthelmintic Triclabendazole and Its Metabolites Inhibit the Membrane Transporter ABCG2/BCRP
Barrera Borja, Otero Jon A., Egido Estefania, Prieto Julio G., Seelig Anna, Alvarez Ana I., Merino Gracia (2012), The Anthelmintic Triclabendazole and Its Metabolites Inhibit the Membrane Transporter ABCG2/BCRP, in ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56(7), 3535-3543.
Thermodynamics of Protein Self-Association and Unfolding. The Case of Apolipoprotein A-I
Zehender F., Ziegler A., Schoenfeld H. -J., Seelig J. (2012), Thermodynamics of Protein Self-Association and Unfolding. The Case of Apolipoprotein A-I, in BIOCHEMISTRY, 51(6), 1269-1280.
Cell Penetrating Peptides. How do they Cross Membranes?
Seelig Joachim, Ziegler Andre, Klocek Gabriela (2011), Cell Penetrating Peptides. How do they Cross Membranes?, in BIOPHYSICAL JOURNAL, 100(3), 494-494.
Contributions of Glycosaminoglycan Binding and Clustering to the Biological Uptake of the Nonamphipathic Cell-Penetrating Peptide WR9
Ziegler Andre, Seelig Joachim (2011), Contributions of Glycosaminoglycan Binding and Clustering to the Biological Uptake of the Nonamphipathic Cell-Penetrating Peptide WR9, in BIOCHEMISTRY, 50(21), 4650-4664.
The ATPase Activity of CFTR Measured in Living Cells
Seelig Anna, Zwick Matthias, Hellstern Manuel (2011), The ATPase Activity of CFTR Measured in Living Cells, in BIOPHYSICAL JOURNAL, 100(3), 246-246.
The ATPase Activity of CFTR Measured in Living Cells
Seelig Anna, Zwick Matthias, Hellstern Manuel (2011), The ATPase Activity of CFTR Measured in Living Cells, in BIOPHYSICAL JOURNAL, 100(3), 246-246.
Thermal phase behavior of DMPG bilayers in aqueous dispersions as revealed by 2H- and 31P-NMR
Loew C, Riske KA, Lamy MT, Seelig J (2011), Thermal phase behavior of DMPG bilayers in aqueous dispersions as revealed by 2H- and 31P-NMR, in Langmuir, 27(16), 10041-10049.
Thermodynamics of lipid interactions with cell-penetrating peptides.
Sauder R, Seelig J, Ziegler A (2011), Thermodynamics of lipid interactions with cell-penetrating peptides., in Methods in molecular biology (Clifton, N.J.), 683, 129-155.
Lipid and peptide dynamics in membranes upon insertion of n-alkyl-β-D-glucopyranosides
Meier M, Seelig J (2010), Lipid and peptide dynamics in membranes upon insertion of n-alkyl-β-D-glucopyranosides, in Biophysical Journal, 98(8), 1529-1538.
On the interaction of ionic detergents with lipid membranes. Thermodynamic comparison of n-alkyl-+N(CH₃)₃ and n-alkyl-SO₄⁻.
Beck Andreas, Li-Blatter Xiaochun, Seelig Anna, Seelig Joachim (2010), On the interaction of ionic detergents with lipid membranes. Thermodynamic comparison of n-alkyl-+N(CH₃)₃ and n-alkyl-SO₄⁻., in The journal of physical chemistry. B, 114(48), 15862-71.

Collaboration

Group / person Country
Types of collaboration
Prof. Michael Bienert, FMP Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Michael Beyermann, FMP Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Yechiel Shai, Weizmann Inst. Israel (Asia)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Jean-Claude Martinou, University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Burkhard Bechinger, University of Strasbourg France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. John R. Riordan, UNC United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Gunda Georg, University of Minnesota United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Kaspar Vogt, Biozentrum Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Kaspar P. Locher, ETH Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
Prof. Geoffrey Chang, Scripps Res. Inst. United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results

Associated projects

Number Title Start Funding scheme
107793 Protein folding in membranes and multiple drug resistance 01.04.2005 Project funding (Div. I-III)

Abstract

Project ACell penetrating peptides have become interesting tools for trans-membrane transport studies and are investigated in pharmacological applications to transport protein and nucleic acids across cellular membranes. Different pathways are possible, ranging from detergent-like diffusion to binding to sulfated glycosamines, coupled with endocytosis. The details of membrane passage will be investigated with chemically modified CPPs to gain insight into the mechanistic details. The proposed modifications include pegylation, acylation with long chain fatty acids, and replacing polar amino acid by non-polar ones. The working hypothesis is to shift the hydrophilic ? amphipathic ? hydrophobic balance and to correlate it with membrane binding and cellular uptake. In a second project we will investigate (i) the membrane-induced random coil <-> beta-structure equilibrium of Alzheimer peptides and (ii) the pH-induced trans-membrane flip of the LAH4 peptide with isothermal titration calorimetry, dynamic light scattering, analytical ultracentrifugation, and spectroscopic methods.Project BDrug absorption across biological membranes is determined by passive influx and active efflux of drugs by ATP binding cassette (ABC transporters). We have investigated both processes with a special emphasis on active efflux by the ABC transporter P-glycoprotein (ABCB1). We developed a new assay that allows measuring the ATPase activity in cells and provided direct evidence for a substrate transporter interaction based on a modular binding principle.
-