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Biomacromolecules副主编Klok学术报告(2013-01-24)

( 2013-01-21 )
 

报告题目

Combating Diseases with Peptide – Synthetic Polymer Conjugates

报告时间

2013124 (星期四) 上午10:00

报告地点

科大东区材料楼五楼会议室

报告摘要

请见附件

报告人

Prof. Harm-Anton Klok

Ecole Polytechnique Fédérale de Lausanne (EPFL) (Lausanne, Switzerland)

 
 
Harm-Anton Klok
Institutes of Materials and Chemical Sciences and Engineering
Ecole Polytechnique Fédérale de Lausanne (EPFL)
Lausanne, Switzerland
Group Website: http://lp.epfl.ch/

 Harm-Anton Klok is Full Professor at the Institutes of Materials and Chemical Sciences and Engineering at the Ecole Polytechnique Fédérale de Lausanne (EPFL) (Lausanne, Switzerland).
He studied chemical technology at the University of Twente (Enschede, The Netherlands) from 1989 to 1993 and received his Ph.D. in 1997 from the University of Ulm (Germany) after working with Martin Möller. After postdoctoral research with David N. Reinhoudt (University of Twente) and Samuel I. Stupp (University of Illinois at Urbana–Champaign, USA), he joined the Max Planck Institute for Polymer Research (Mainz, Germany) in early 1999 as a project leader in the group of Klaus Müllen. In November 2002, he was appointed to the faculty of EPFL.

His current research interests include peptide/protein-based materials and peptide/protein-polymer hybrids, surface-initiated polymerization and polymer brushes, controlled/”living” polymerization and macromolecular engineering as well as dendritic and hyperbranched polymers.

Harm-Anton Klok is recipient of the 2007 Arthur K. Doolittle Award of the American Chemical Society and is Associate Editor of the American Chemical Society journal Biomacromolecules. He serves on the editorial advisory board of European Polymer Journal, Journal of Polymer Science A: Polymer Chemistry, Macromolecules, ACS Macro Letters as well as Macromolecular Rapid Communications and Macromolecular Bioscience. Harm-Anton Klok has been a Visiting Professor at the University of Bordeaux (France) in 2010, the University of Massachusetts / Amherst (USA) in 2012, has been nominated as Chair Professor, College of Chemistry, Chemical Engineering and Materials Science, Soochow University (Suzhou, China) in 2011, is a guest professor at the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun (China) since 2012 and was awarded a Chinese Academy of Sciences visiting professorship for senior international scientists (Institute of Chemistry, Chinese Academy of Sciences, Beijing) for 2012 - 2013.
 
 
 

Combating Diseases with Peptide – Synthetic Polymer Conjugates

 

Harm-Anton Klok

Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut des Matériaux and Institut des Sciences et Ingénierie Chimiques, Laboratoire des Polymères, Station 12, CH-1015 Lausanne (Switzerland). E-mail : harm-anton.klok@epfl.ch

 

Peptides and proteins often combine unique self-assembly properties with very specific biological activities. From a therapeutic point of view, peptides and proteins are of interest, not only because of the possibilities to act as inhibitors or antagonists of biological processes (i.e. to act as therapeutics), but also because they provide opportunities e.g. for targeted delivery or to guide intracellular trafficking. Judiciously combining biologically active peptides or proteins with synthetic polymers provides opportunities to overcome problems related to the limited stability and plasma half life of peptides and proteins, to enhance the efficacy of polymer-drug conjugates and to augment the activity of peptide based therapeutics.[1-4] This presentation will consist of three parts which will successively discuss: (i) non-covalent polymer – drug conjugates in which the peptide-based linker not only acts to bind and release cargo but is also involved in directing intracellular trafficking;[5,6] (ii) polymer-modified HIV fusion inhibitors that show increased stabilities as compared to the unmodified peptides while maintaining activity[7] and (iii) multivalent HIV entry inhibitors based on side-chain peptide – polymer conjugates which allow to augment the activity of the peptide.[8] In all three cases, precision polymer synthesis is essential in the successful design of the final conjugates. Amongst others, the examples will highlight the importance of controlling molecular weight, the site of polymer – peptide conjugation as well as polymer architecture on the final properties and activities of the peptide – polymer conjugates.

 

References: 

[1] M. A. Gauthier, H.-A. Klok, Peptide/protein – polymer conjugates: synthetic strategies and design concepts, Chem. Commun. (2008) 2591 – 2611.

[2] H.-A. Klok, Peptide/protein – synthetic polymer conjugates – Quo vadis, Macromolecules 42 (2009) 7990 – 8000.

[3] B. Apostolovic, M. Danial, H.-A. Klok, Coiled coils: attractive protein folding motifs for the fabrication of self-assembled, responsive and bioactive materials, Chem. Soc. Rev. 39 (2010) 3541 – 3575.

[4] M. A. Gauthier, H.-A. Klok, Polymer-protein conjugates: an enzymatic activity perspective, Polym. Chem. 1 (2010) 1352 – 1373.

[5] B. Apostolovic, S. P. E. Deacon, R. Duncan, H.-A. Klok, Hybrid polymer therapeutics incorporating bioresponsive, coiled coil peptide linkers, Biomacromolecules 11 (2010) 1187 - 1195.

[6] B. Apostolovic, S. P. E. Deacon, R. Duncan, H.-A. Klok, Cell uptake and trafficking behavior of non-covalent, coiled-coil based polymer-drug conjugates, Macromol. Rapid Commun. 32 (2011) 11 – 18.

[7] M. Danial, T. H. H. van Dulmen, J. Aleksandrowicz, A. J. G. Pötgens, H.-A. Klok, Site-specific PEGylation of HR2 peptides: effects of PEG conjugation position and chain length on HIV-1 membrane fusion inhibition and proteolytic degradation, Bioconjugate Chem. 23 (2012) 1648 – 1660.

[8] M. Danial, M. J. Root, H.-A. Klok, Polyvalent side chain peptide – synthetic polymer conjugates as HIV-1 entry inhibitors, Biomacromolecules 13 (2012) 1438 – 1447.

 

 

Interactive and responsive polymer brushes prepared via surface-initiated polymerization

 

Harm-Anton Klok

Ecole Polytechnique Fédérale de Lausanne (EPFL)

Institut des Matériaux and Institut des Sciences et Ingénierie Chimiques

Laboratoire des Polymères, STI-IMX-LP, MXD 112 (Bâtiment MXD)

Station 12, CH-1015 Lausanne (Switzerland)

E-mail:harm-anton.klok@epfl.ch

 

This presentation will discuss the preparation and properties of interactive and responsive polymer brushes prepared via post-polymerization modification of reactive precursor films that are obtained via surface-initiated controlled radical polymerization.1 After discussing different post-polymerization modification strategies and the characterization of the location and distribution of functional groups in such ultrathin coatings,2,3,4 their use for the fabrication of bioactive surface coatings,5,6 functional films for microarray7,8 or sensory applications9,10will be discussed.

 

References

(1)  Barbey, R.; Lavanant, L.; Paripovic, D.; Schüwer, N.; Sugnaux, C.; Tugulu, S.; Klok, H.-A. Polymer brushes via surface-initiated controlled radical polymerization: synthesis, characterization, properties and applications, Chem. Rev. 2009, 109, 5437 – 5527.

(2)  Günay, K. A.; Schüwer, N.; Klok, H.-A. Synthesis and post-polymerization modification of poly(pentafluorophenyl methacrylate) brushes, Polymer Chemistry 2012, 3, 2186 – 2192.

(3)  Schüwer, N.; Klok, H.-A. Tuning the pH sensitivity of poly(methacrylic acid) brushes, Langmuir 2011, 27, 4789 – 4796.

(4)  Schüwer, N.; Geue, T.; Hinestrosa, J. P.; Klok, H.-A. Neutron reflectivity study on the postpolymerization modification of poly(2-hydroxyethyl methacrylate) brushes, Macromolecules 2011, 44, 6868 – 6874.

(5)  Tugulu, S.; Silacci, P.; Stergiopulos, N.; Klok, H.-A. RGD-functionalized polymer brushes as substrates for the integrin specific adhesion of human umbilical vein endothelial cells, Biomaterials 2007, 28, 2536 – 2546.

(6)  Tugulu, S.; Klok, H.-A. Stability and nonfouling properties of poly(poly(ethylene glycol) methacrylate) brushes under cell culture conditions, Biomacromolecules 2008, 9, 906 – 912.

(7)  Barbey, R.; Klok H.-A. Room temperature, aqueous post-polymerization modification of glycidyl methacrylate-containing polymer brushes prepared via surface-initiated atom transfer radical polymerization, Langmuir 2010, 26, 18219 – 18230.

(8)  Barbey, R.; Kauffmann, E.; Ehrat, M.; Klok, H.-A Protein microarrays based on polymer brushes prepared via surface-initiated atom transfer radical polymerization, Biomacromolecules 2010, 11, 3467 – 3479.

(9)  Schüwer, N.; Klok, H.-A. A potassium-selective quartz crystal microbalance sensor based on crown-ether functionalized polymer brushes, Adv. Mater. 2010, 22, 3251 – 3255.

(10)Schüwer, N.; Tercier-Waeber, M.-L.; Danial, M.; Klok, H.-A. Voltammetric detection of Hg2+ using peptide functionalized polymer brushes, Aust. J. Chem. 2012, 65, 1104–1109.


 
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