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From Bee Venom to Blood-Brain Barrier Shuttles

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From Bee Venom to Blood-Brain Barrier Shuttles From bee venom to blood-brain barrier shuttles. Development of minimized apamin derivatives for brain delivery of antibodies and other cargoes Benjamí Oller Salvia ADVERTIMENT. La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX (www.tdx.cat) i a través del Dipòsit Digital de la UB (diposit.ub.edu) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposició des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB. No s’autoritza la presentació del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. 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Benjamí Oller Salvia 2015 Tesi doctoral Benjamí Oller Salvi Oller Benjamí doctoral Tesi 2015 Programa de doctorat de química orgànica From bee venom to blood-brain barrier shuttles. Development of minimized apamin derivatives for brain delivery of antibodies and other cargoes. Benjamí Oller Salvia Tesi doctoral dirigida per: Prof. Ernest Giralt Lledó Dra. Meritxell Teixidó Turà Universitat de Barcelona IRB Barcelona Facultat de Química Programa de química Departament de Química Orgànica i farmacologia molecular Barcelona, 2015. Als meus pares, als meus avis i a la Irene. Acknowledgements Foremost, I would like to acknowledge my thesis directors Prof. Ernest Giralt and Dr. Meritxell Teixidó for their enthusiasm, guidance and encouragement. I am also deeply grateful to Dr. Macarena Sánchez, with whom I have worked side by side so many hours and who was always ready to lend a helping hand. I also acknowledge all the other people working in Prof. Giralt’s laboratory and all my colleagues at IRB Barcelona, who provided a convivial atmosphere to enjoy working and learning. Especially, I would like to give prominence to the people that have contributed to some extent to the present work, namely Dr. Roger Prades, Dr. Bernat Guixer, Dr. Michael Goldflam, Sonia Ciudad, Pol Arranz, Cristina Díaz, Josep Garcia and Cristina Garcia. In this regard, I also acknowledge our collaborators and other scientists who have participated in some experiments, including Dr. Roger Gomis, Dr. Joan Seoane, Dr. Maria del Mar Inda, Josep Calderón, Marc Guiu and Nuno Vasconcelos. And how could I forget the two people that helped me discover IRB and Prof. Giralt’s laboratory: Dr. Joan Serratosa and my longtime friend Sílvia Vilaprinyó. During these years I had the chance to benefit from several research stages abroad, which have undoubtedly enriched the overall experience of my thesis. I would like to acknowledge all the supervisors and scientists that made it possible. First I would like to thank Prof. Kai Johnsson for allowing me to perform a 3-month research stage in his laboratory at EPFL; I would like to emphasize my gratefulness to the invaluable help of Dr. Grazvydas Lukinavicius and to all the other people in the laboratory for providing an outstanding working atmosphere. I would also like to acknowledge Prof. Dario Neri for making it possible to go to his laboratory at ETH. I could not forget the fruitful trainings by Emmanuel Sevin and Stéphane Nion in Prof. Romeo Cecchelli laboratory at Université d’Artois. Finally, I would like to thank Prof. Elazer Edelman and Prof. Mercedes Balcells, at MIT, with whom I first worked on BBB models. Lastly, but not less important, I am at a loss for words to convey my infinite gratitude to my parents, grandparents and Irene for their limitless patience and unconditional support. The present work was performed at IRB Barcelona with the financial support of “La Caixa”/IRB fellowship. Unus pro omnibus, omnes pro uno. 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