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Induction of structure and function in a designed peptide upon adsorption on a silica nanoparticle
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Molecular Biotechnology. Linköping University, The Institute of Technology.
Linköping University, Department of Physics, Chemistry and Biology, Applied Optics . Linköping University, The Institute of Technology.
2006 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 45, no 48, 8169-8173 p.Article in journal (Refereed) Published
Abstract [en]

No abstrack available.

Place, publisher, year, edition, pages
2006. Vol. 45, no 48, 8169-8173 p.
Keyword [en]
Amino acids, catalysis, helical structures, nanoparticles, peptides
National Category
Chemical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14548DOI: 10.1002/anie.200600965OAI: oai:DiVA.org:liu-14548DiVA: diva2:23691
Available from: 2008-02-25 Created: 2008-02-25 Last updated: 2012-11-16Bibliographically approved
In thesis
1. De Novo Design and Characterization of Surface Binding Peptides - Steps toward Functional Surfaces
Open this publication in new window or tab >>De Novo Design and Characterization of Surface Binding Peptides - Steps toward Functional Surfaces
2006 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

The ability to create surfaces with well-defined chemical properties is a major research field. One possibility to do this is to design peptides that bind with a specific secondary structure to silica nanoparticles. The peptides discussed in this thesis are constructed to be random coil in solution, but are “forced” to become helical when adsorbed to the particles. The positively charged side-chains on the peptides strongly disfavor an ordered structure in solution due to electrostatic repulsion. When the peptides are introduced to the particles these charges will strongly favor the structure because of ion pair bonding between the peptide and the negatively charged nanoparticles. The peptide-nanoparticle system has been thoroughly investigated by systematic variations of the side-chains. In order to determine which factors that contributes to the induced structure, several peptides with different amino acid sequences have been synthesized. Factors that have been investigated include 1) the positive charge density, 2) distribution of positive charges, 3) negative charge density, 4) increasing hydrophobicity, 5) peptide length, and 6) by incorporating amino acids with different helix propensities. Moreover, pH dependence and the effect of different nanoparticle curvature have also been investigated. It will also be shown that the system can be modified to incorporate a catalytic site that is only active when the helix is formed. This research will increase our understanding of peptide-surface interactions and might be of importance for both nanotechnology and medicine.

Place, publisher, year, edition, pages
Institutionen för fysik, kemi och biologi, 2006. 51 p.
Series
Linköping Studies in Science and Technology. Thesis, ISSN 0280-7971 ; 1254
Keyword
Peptide, design, nanoparticle, CD, Amino acid
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-8992 (URN)91-85523-57-7 (ISBN)
Presentation
2006-06-16, Nobel, B-huset, Linköpings universitet, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2008-02-25 Created: 2008-02-25 Last updated: 2009-03-09
2. Structural and Functional Studies of De Novo Designed Peptides at Surfaces
Open this publication in new window or tab >>Structural and Functional Studies of De Novo Designed Peptides at Surfaces
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The work presented in this thesis deals with the structural and functional properties of peptides at surfaces. The interaction of peptides with surfaces is an ever so common occurrence in our every day life, from the bug squashed on the windshield of our car to the barnacle on our boat, and from the blood plasma used in the hospital to the proteins in our cells. The effect these occurrences has on our lives is diverse, the bug is annoying whereas the barnacle settlement of ship hull is costly for marine transportation, the blood plasma contains components of vital importance for our immunological defense system and the proteins in our cells are crucial for regulatory processes and life.One part of this thesis, performed as a part of the EU-founded project AMBIO, deals with the concept of marine biofouling. A number of short peptides have been designed, synthesized, and used to investigate their effect on the settlement on marine biofoulers, such as the Ulva linza algae and the Navicula diatom, on template surfaces coated with thin layers of these molecules. The surfaces have been thoroughly investigated with respect of their physio-chemical properties before and after submersion in artificial seawater and ultimately in suspensions containing the organisms. The most interesting results were obtained with an arginine-rich peptide coating that when introduced to Ulva linza zoospores, displayed extensive settlement, compared to reference surfaces. In addition, a large fraction of the settled spores had an abnormal morphology.The other part of this thesis is focused on designed peptides that when adsorbed on a negatively charged surface adopts a well-defined secondary structure, either α-helical or β-sheet. Precisely placed amino acids in the peptides will strongly disfavor structure in solution, primarily due to electrostatic repulsion, but when the peptides are adsorbed on the negatively charged surfaces, they adopt a well-defined secondary structure due to ion pair bonding. These interactions have been thoroughly investigated by systematic variations of the side-chains. In order to determine the factors contributing to the induced structure, several peptides with different amino acid sequences have been synthesized. Factors that have been investigated include 1) the positive charge density, 2) distribution of positive charges, 3) negative charge density, 4) increasing hydrophobicity, and 5) incorporating amino acids with different helix propensities. Moreover, pH dependence and the effect of different interaction partners have also been investigated. It has also been shown that the system can be modified to incorporate a catalytic site that is only active when the helix is formed. This research will increase our understanding of peptide-surface interactions and might be of importance for both bionanotechnology and medicine.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 52 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1199
Keyword
Biofouling, vesicles, nanoparticles, peptide, peptide design, circular dichroism
National Category
Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-15022 (URN)978-91-7393-840-2 (ISBN)
Public defence
2008-09-05, Planck, Campus Valla, Linköpings universitet, Linköping, 10:15 (English)
Opponent
Supervisors
Available from: 2008-10-09 Created: 2008-10-09 Last updated: 2017-01-11Bibliographically approved
3. Conformation of polypeptides at nanoparticles interfaces: protein structural changes and induced folding of peptides
Open this publication in new window or tab >>Conformation of polypeptides at nanoparticles interfaces: protein structural changes and induced folding of peptides
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis can be divided into two parts. The first deals with characterization of structural and dynamic consequences for proteins of interactions with a solid surface in the form of silica nanoparticles. The studies were conducted on isoenzymes and mutant variants of Human Carbonic Anhydrase that have virtually identical topology but differ considerably with respect to stability. The nanoparticles were chosen as the solid phase because their small sizes allow the use of spectroscopic techniques that are usually employed to study molecular interactions in solution.

CD measurements of the interactions between HCAI and nanoparticles with different diameters show that the perturbation of the secondary structure is dependent on the curvature of the nanoparticle. A relatively flat surface causes greater perturbation because it allows a larger interaction area with the. protein than a curved surface. Use of the TROSY pulse sequence allowed NMR spectra of a large stable complex of HCAII and solid nanoparticles to be recorded. The NMR study confirmed earlier conclusions based on CD measurements that HCAII undergoes major structural rearrangements upon binding to the nanoparticles and that the protein continues to rearrange for at least two weeks after binding. Sedimentation equilibrium AUC and gel permeation chromatography experiments established that HCAI is in a true equilibrium between forms that are free and forms that are bound to the nanoparticles for at least seven days. NMR studies of HCAI-nanoparticle systems showed that residues in the central ß-strands of HCAI do not regain their native conformation during the time they are dissociated from the nanoparticles i.e. information about the bound state were gleaned from studies of free molecules. Further NMR studies showed that the perturbations persist for long time even after removal of the nanoparticles from the solution. Surprisingly, the conformational heterogeneity did not disturb the delicate positioning of the active site residues that is required for full catalytic activity. A novel approach was used to characterize the initial binding of HCAII to the nanoparticles and subsequent structural alterations of the protein. MALDI-TOP mass spectrometry was used to analyse the fragment patterns after proteolytic cleavage in the presence of nanoparticles and the results were compared with corresponding fragment pattern for a native sample. The initial binding site of HCAII was shown to include parts of the N- and C-termini and the major subsequent structural rearrangements were also characterized.

The second part of this thesis concerns an approach to use surface interaction to regulate the structure and function of designed peptides. Using de novo design, a peptide was constructed that would be unstructured in solution, but would be "forced" to adopt a well-defmed helical structure following adsorption to silica nanoparticles. Moreover, the design also included precisely placed amino acids that were intended to form a functional catalytic site upon induction of the helix on the surface of the nanoparticles. Characterization of the structure and function of the designed peptide using CD and activity measurements show that the nanoparticles can be used, as intended, to induce structure in the peptide and switch on the catalytic function.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2005. 49 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 926
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-24573 (URN)6746 (Local ID)91-852-9749-6 (ISBN)6746 (Archive number)6746 (OAI)
Public defence
2005-03-11, Planck, Fysikhuset, Linköpings Universitet, Linköping, 09:15 (Swedish)
Opponent
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2012-11-16

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Lundqvist, MartinNygren, PatrikJonsson, Bengt-HaraldBroo, Klas

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