THESE DE DOCTORAT DE
L'UNIVERSITE DE NANTES COMUE UNIVERSITE BRETAGNE LOIRE ECOLE DOCTORALE N° 605 Biologie Santé
UNIVERSIDAD SANTIAGO DE COMPOSTELA ESPAGNE
Par Petar VUKOJICIC
« Affitin-dendrimer conjugates for multivalency-enhanced targeting »
Thèse présentée et soutenue à Nantes, le 28 Janvier 2019 Unité de recherche : CRCINA U1232 CIQUS
Rapporteurs avant soutenance :
Jan Van HEST Professeur, Eindhoven University of Technology Michael MALKOCH Professeur, Royal Institute of Technology (KTH)
Composition du Jury : Président : Elena ISHOW Professeur, Université de Nantes Examinateur : Patrice SOUMILLION Professeur, Université catholique 0de Louvain Dir. de thèse : Barbara MOURATOU Maitre de conférences, Université de Nantes Co-dir. de thèse : Eduardo FERNANDEZ-MEGIA Professeur, Universidad Santiago de Compostela
Mom ocu i mojoj baki, u ime večnog zaveta koji sam im dao.
(To my father and my grandmother, in the name of the pledge I made.)
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Table of contents
Acknowledgements………………………………………………………………...... 3
Synopsis.……………………………………………………………………………………………………6
Abbreviations…………………………………………………………………………………………….9
Chapter I: Introduction…………………………………………………………………………….13
Chapter II: Objectives……………………………………………………………………………..102
Chapter III: Synthesis and characterization of Affitin-dendrimer conjugates for multivalent targeting of Staphylococcus aureus Protein A…………………107
Chapter IV: Interaction of Affitin-dendrimer conjugates with Staphylococcus aureus…………………………………………………………………….…………………………..…170
Chapter V: Conclusions and perspectives………………………………………………..202
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Acknowledgements
The work presented in the following pages is an achievement of my family, friends, coworkers and mentors whose vast, selfless support kept my hand steady in the most difficult of times. No words can fully express the gratitude I feel towards this amazing group of people that I am proud to call my own.
Firstly, I need to express deep appreciation to my supervisors Dr
Barbara Mouratou and Dr Eduardo Fernandez-Megia for the opportunity to work with them and benefit from their knowledge, experience and leadership. Their persistent confidence in me, along with the support in all professional and personal affairs, made all the difference.
I would like to thank the members of thesis committee Dr Jean-
Francois Gestin and Dr Anxo Vidal for important insights and stimulating discussions during our meetings. I am also grateful to the members of the jury for my thesis defense Dr Jan Van Hest, Dr Michael Malkoch, Dr Elena
Ishow and Dr Patrice Soumillion for agreeing to evaluate this work.
During the last years, I was fortunate to work in three different countries and three different laboratories. First, I want to thank my group in
France: Fred and Axelle, who always had the most patience to discuss my work in detail in our meetings, inspiring and providing innovative perspectives and thus improving the quality of my research immensely;
Ghislaine, whose invaluable experience in the laboratory is exceeded only
3 by her kindness, selflessness and willingness to help; my peers Stanimir,
Valentina and Benjamin with whom I have shared everything and who will always stay in the circle of my closest friends. Furthermore, I thank other members of Team 13 and Unit 1232 who supported me – Michel, Stephanie,
Bertrand, Stephan, Mike,