Protein surface recognition by polymers [Elektronische Ressource] / by Wei Sun

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• Publié par: universitat_duisburg-essen
• Publié le: 01 janvier 2009
• Nombre de lectures: 32
• Langue: English
• Poids de l'ouvrage: 2 Mo

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Protein Surface Recognition by
Polymers


Dissertation

by
Wei Sun



Essen, 2009

Protein Surface Recognition by
Polymers


Dissertation

by
Wei Sun
Birth Place: Shenyang / China


In Partial Fulfillment of the
Requirements for the Degree
Doctor of Chemistry
(Dr. rer. nat.)


Department of Chemistry
University Duisburg-Essen

January, 2009






























This work is submitted at 30th January, 2009 and is accepted at 24th February, 2009 by the
department of chemistry in the university of Duisburg-Essen in Germany. The oral defence is
tat 24 h March, 2009.

Chairman: Prof. Dr. Stephan Shulz
Reviewer: Prof. Dr. Thomas Schrader
Reviewer: Prof. Dr. Mathias Ulbricht
























To my family




















This work was performed during the period from October 2005 to August 2006 at the institute
of organic chemistry, University Marburg, and from September 2006 to January 2009 at the
institute of organic chemistry, University Duisburg-Essen, under the supervision of Prof. Dr.
Thomas Schrader.


I declare that this dissertation represents my own work, except where due acknowledgement
is made.



Wei Sun

Eidesstattliche Erklärung

Hiermit versichere ich, die vorliegende Arbeit mit dem Titel

„ Protein Surface Recognition by polymers „

selbst verfasst und keine ausser den angegebenen Hifsmitteln und Quellen verwendet zu
haben.

Zudem erkläre ich, dass ich die Arbeit in dieser order ähnlicher Form bei Keiner anderen
Fakultät eingereicht habe.


Essen, im Janur 2009,



Wei Sun Acknowledgement

A number of colleagues, friends, and family members are instrumental in helping me
complete my Ph.D. research and deserve proper thanks. First and foremost, I would like to
pay my gratitude to Prof. Dr. Thomas Schrader for providing this interesting project and for
his supervision. His kind support in other parts of life is also, highly acknowledged.

I am thankful to Prof. Dr. Mathias Ulbricht for reviewing my thesis.

I am also indebted to all members of my research group for their friendship and help.
Especially, I would like to thank Christian Renner, Kirstian Wenck, Marc Blecking, Caroline
Breitkreuz, for their kind suggestions in my work and friendly help during my living in
Marburg and Essen. I would also like to thank Heinz Bandmann and Dr. Torsten Schaller for
the NMR measurement; Heike woell for the HPLC, Film balance measurement and peptide
synthesis; Ingeborg Reiter for her kind advices and help; Klaus Kowoski for the ITC
measurement.

I would like to thank all the technical departments in the university of Duisburg-Essen,
especially the MS department for the mass spectrum measurement, and Dieter Jacobi for the
GPC measurement. The same thank goes to all the technical departments in the University of
Marburg for their help during my first year Ph.D study there.

I would like to thank Prof. Dr. Börje Sellergren and Dr. Eric Schillinger for their kind
cooperation.

Last but not least, I would like to thank my family, especially my wife, Jing Xu. Without their
loving guidance, encouragement, and support, I would certainly not have been capable of
enduring a Ph.D. degree program. Abstract

Recognition of protein surfaces using synthetic receptors is an effective strategy for providing
access to enzyme inhibitors, protein antagonists, and diagnostic biosensors. In the artificial
protein receptors, polymers represent promising fields due to their sizes (commensurate with
proteins) and the ability to tailor a wide range of functionalities. Furthermore, the ability of
polymers to adapt their conformations to protein surfaces renders them attractive candidates for
protein surface binding.

This work emphasized firstly on the synthesis of functional monomers which are specific for
the amino acid residues on protein surfaces, and then on the development of polymers which
can recognize protein surfaces in aqueous solution tightly and selectively.

Eighteen monomers were prepared by multi-step synthesis. The interactions between their
functional groups and amino acid residues covered several binding motifs in molecular
recognition: hydrogen bond, electrostatic, hydrophobic, metal-ligand and π-cation interaction.
For the later polymerization, these functional groups were incorporated with polymerizable
structures. Thirteen of them were based on methylacylamide, and the other five were based on a
10, 12- tricosadiyne structure.

Functional monomers based on methylacrylamide were polymerized by radical polymerization
under heat or UV light in organic solvent or aqueous solution, with AIBN, V-50, benzophenone
or ammonium persulfate as initiators. In some cases polymer lengths were controlled by RAFT
method with water-soluble S, S´-bis(α,α’- dimethyl- α’’acetic acid)-trithiocarbonate as the
chain transfer reagent (CTA) in aqueous buffer. Functional monomers based on a 10, 12-
tricosadiyne structure composed of two parts: a polar functional headgroup and a hydrophobic
tail containing the diacetylene moiety. The polymerization could proceed without any initiator,
only when the diacetylenes were arranged in a lattice with appropriate geometry, ex., at
water-air surface or in the form of liposome.