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University of Groningen Stapled peptides inhibitors Ali, Amina

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University of Groningen

Stapled peptides inhibitors Ali, Amina

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2019

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Ali, A. (2019). Stapled peptides inhibitors: A new window for target drug discovery. University of Groningen.

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Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum.

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It’s been a long road, but here I am at the end; it is a humbling experience to acknowledge those people who have helped along the journey of my PhD. I am indebted to a large number of people for encouragement, kind efforts and support that enabled me to compile and write this thesis. This thesis is also the result of many experiences I have encountered at Groningen University from dozens of remarkable individuals who I also wish to acknowledge.

Beginning with the most important and unending source of support: my Mum, Nawal Althawadi, I can describe my relation with her as the best ever part in my whole life, she is a friend more than a parent to me and I am honored to make your dream coming true; to be Dr. Ameena Ali. I extend my very profound gratitude to my Dad, Mohammed Ali, for his trust and believing in me to face my destiny a broad, for my sisters, Thajba, Lulwa and Duha, for providing me with unfailing support and continuous encouragement throughout my years of study. For the presence of my brothers, Ali and Jassim, your screams of joy whenever a significant moment was reached and also your supportive hugs. Your prayer for me was what sustained me thus far.

Moving to my-life coach, Jack Atmaj, I owe it all to you. Jack is indescribable person in my life since we meet in Feb 2015 at Groningen University, a great partner in work and life. Thank you for sharing me the marvelous MDM2-p53 project, which we did together. Thanks for sharing ideas, experience and discussion besides the unconditional faithful support; encouraging, and patient throughout all the stages of this Ph.D. This accomplishment would not have been possible without you. You have cherished with me every great moment and endorse me whenever I needed it.

My miracle sisters in my whole life, Hobab, Noura, and Lolwa, you were continually in my back whispering, “You can do it”. The heart-warming support, which you were all provided, combined with the straightforward criticism, given me great confidence as a researcher and Doctor titleholder. You have always been there for me my best friends.

Professionally, first and foremost I would like to thank my three advisors, Prof. Alexander Domling, The Chair of Drug Design and the Head of the Department- Groningen University, for providing me the opportunity to join his team as a Ph.D. student and for his encouraging in my research. Your humble personality and sense of humor beside your massive expertise and knowledge, let me felt home. Two words will always be remembered from our memories are “Dr. Ali and InshaAlex!!”. Dr. Matthew Groves, Assistance Professor in Drug Design Group- Groningen University, I am grateful for your tremendous support and for allowing me to grow as a research scientist. Your advice on both research as well as on my career have been priceless. We went through many situations together, we struggled, we lost temper, we laughed and we live the glory. You were in the moments when there was no one to answer my queries. As a researcher, I appreciate your faith on my work and me; you never left my hand during the times when I was really down. My sincere gratitude is reserved for Dr. Sayed Goda, Senior Research Scientist in ADLQ- Qatar. It was an amazing fate when we decide to work together as primary supervisor and Ph.D. student. I am very thankful for introducing me to Prof. Alexander to start my PhD; it was a real privilege and an honor for me when you called me “Your partner”.

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I would like to acknowledge the members of the reading committee: Prof. Gerrit Poelarends and Prof. Frak Dekker from the University of Groningen, Prof. Stefan Knapp from Oxford University for their time and efforts to evaluate and approve this thesis, also for their valuable comments and interest in my work.

A very special gratitude goes out to my sponsor, Qatar Leadership Program, Qatar foundation for their financial support and kind thoughtful of me as broad student, you have given me the chance to make my dream true. With a special mention to Dr. Ayman Basil and Dr. Aisha Al-Obaidly for their intimate support and follow-up, for the time to meet me, for the fast reply to my question or query and being beside me as PhD-sponsored student regardless of distance.

I was fortunate to have the chance to work with Prof. Tad Holak, Group leader of Chemical Biology and Drug Discovery, Jagiellonian University- Poland, and Dr. Aleksandra Twarda; I appreciate your hospitality and friendly hosting that you showed during my research work within your group and for sharing knowledge related to Mdm2 project. From Cuba, Dr. Daniel García Rivera (Director Center for Natural Products Studies, University of Havana), I was lucky to work with MDM2-p53 stapled peptides, those compounds were the first to conduct my MST assay for the binding affinities assessment and the first compounds that gave me a successful crystals out of many failed co-crystallization trials; they were the hope light despite all the darkness. Dr. Chris Williams (Group leader of Molecular Cell Biology) for engaging me in the Pexs project, I worked (nonstop) in this project and overcome all the challenges that faced me, I have learned a lot morally and professionally, which I am thankful for. Your project opens the door for publications.

I am also deeply thankful to many experts from different faculties at the RUG, Dr. Ykelien Boersma, Dr. Robbert Cool and Dr. Hannah Wapenaar from Department of Chemical and Pharmaceutical Biology. Your kind support helped me to pursue my protein purification experiments, without it I am certain my life in the lab will be more challenging. A heartfelt thanks to the supportive Natasha Danda not only for her useful suggestions, but also for being there to listen when I needed an ear. The last, not the least, the stylish-inventor Jean-Paul Mudler from Pharmaceutical Analysis research group, we never worked together but you have been the light shadowed neighbor who draw smile one everyone face with your open-hearted stories, jokes and even complaining, as you describe your-self “The best Technician Ever!!”

PhD students often talk about loneliness during the course of their study but this is something, which I never experienced at Structural Biology Group. We came from different cultures and backgrounds but I believed we mixed together in harmonic way. My colleagues who went above the call of duty in making things in the lab run by undertaking the most horrifying tasks at cleanup. Among the most helpful were our Kai, I know you can do it, Fernando “Lets cry together” sometime you are unpredictable, my lovely & dearest Wenja, you have a pure soul my friend, and Chao, thanks for keep smiling, Juliana, we work together in the last year of my PhD but I am glad for your help, replying my Whatsup messages anytime and your tips when I struggle with Pymol.

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I am also hugely appreciative to the Chemistry group, our magical compounds makers, I would like to thanks Dr. Eman Abdelraheem for her advice, listening to my complains and for providing me with the macocycle compounds, Dr. Dinos “Constantinos G. Neochoritis” for providing me with the small-molecules compounds for MDM2 screening and co-crystallization. It was an extremely nice experience to work with both of you.

Last but not least, the group would have been a much less consistent unit and the lab would have been a less enjoyable place without some people, I have to mention here Niels van Oosterwijk “the Prof.”. Thank you for providing invaluable guidance throughout Pexs research work and MDM2 project specifically by sharing with me your experience in Crystallography and solving protein-structures. Your dynamism and authenticity have deeply inspired me. It was a great privilege to work with you and to be your student. I am extremely grateful for your friendship, empathy, and great sense of humor.

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