University of Groningen
Structure-Function Relationships in Dynamic Combinatorial Libraries
Altay, Meniz
DOI:
10.33612/diss.90038152
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Publication date: 2019
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Altay, M. (2019). Structure-Function Relationships in Dynamic Combinatorial Libraries. University of Groningen. https://doi.org/10.33612/diss.90038152
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214 Samenvatting vezels uit enkele entvezels. In het laatste deel van dit hoofdstuk doen we verslag van onze pogingen om de blokvezels direct te visualiseren met behulp van elektronenmi-croscopie door halogenen in de bouwstenen te introduceren.
De meeste bouwstenen die in onze groep zijn ontwikkeld bestaan uit een aroma-tische kern met twee thiolgroepe en een kort peptide dat een b-sheet vormt, waar-van het eerste aminozuur als een spacer werkt. In hoofdstuk 3 laten we zien hoe zelf-replicatie kan worden afgesteld door de lengte van de spacer te veranderen, in DCLs gemaakt van twee structureel verschillende bouwstenen waarin β-alanine en γ-aminoboterzuur als spacer zijn opgenomen. Na aanpassing van de bouwstenen met deze aminozuren, die extra methyleen-groepen bevatten ten opzichte van de oor-spronkelijke glycine spacer, onderzochten we het zelfreplicatiegedrag van mutanten in verschillende omstandigheden. We laten de opkomst van zelfreplicatoren van ver-schillende grootte zien uit de mutanten van de eerste bouwsteen en remming van de zelfreplicatie in DCLs gemaakt van de mutanten van de tweede bouwsteen.
Op een vergelijkbare manier ontdekten we in hoofdstuk 4 parasitair gedrag tussen zelfreplicatoren die gevormd werden uit bouwstenen die verschillen door slechts een enkele methyleengroep. We merkten op dat een 6-ring replicator alleen kan ontstaan wanneer deze wordt ondersteund door een reeds bestaande 8-ring zelfreplica-tor. Terwijl de 8-ringen optraden als sjabloon voor de vorming van hexamere soorten aan het ene uiteinde van de vezel, werden ze zelf van het andere uiteinde afgebroken tot het punt dat ze aan het einde van het experiment niet langer detecteerbaar waren. We hebben ook experimenteel bewijs geleverd voor de eenrichtings-kruiskatalyse tussen de zelfreplicatoren: 8-ringen kunnen de vorming van 6-ringsoorten kataly-seren, maar niet omgekeerd.
Met het oog op diversificatie van zelfreplicatoren door middel van een kruiskat-alytische route onder out-from-equilibrium condities, hebben we in hoofdstuk 5 continue-flow opstellingen gebruikt. Door gebruik te maken van de eerste reeks bouw-stenen die in hoofdstuk 3 werden bestudeerd, hebben we mengsels van monomeren, trimeren en tetrameren met verschillende bouwbloksamenstellingen in een oplossing met zelfreplicatoren geecteerd en hun adaptatie gevolgd als functie van tijd. Eerst hebben we een systeem met twee bouwstenen opgezet en de experimentele condities geoptimaliseerd betreffende doorstroomsnelheid, tijd en initi replicatorsamenstelling. We rapporteren ook pogingen om een cross-catalytische cyclus te cren door de intro-ductie van een derde bouwsteen. We hebben na verloop van tijd een verandering in de grootte van de replicatoren waargenomen. Voor een meer gedetailleerde kinetische analyse is echter een verdere optimalisatie van de analysemethoden vereist.
Tot slot worden ons onderzoek in hoofdstuk 6 in een breder perspectief geplaatst en worden de toekomstperspectieven besproken.
Acknowledgements
Dear Sijbren, I would like to thank you for giving me the opportunity to work in your group. I appreciate your way of giving freedom to people in their research projects. Overall, I learned a lot of scientifically and personally valuable things from you which helped me to become a better researcher and a better person. Thank you for all your contributions.
I would like to thank to the reading committee, Prof. Martin Witte, Prof. Rint Sijbesma and Prof. Michael Pittelkow for their time to read my thesis and insightful comments and corrections.
I am grateful to Monique and Theodora for their scientific support in chromatog-raphy and spectrometry related issues and Annette for her helps in all administrative issues. And Marc, thank you for introducing me to the amazing world of electron microscopy. I have always admired your approach to problems, your efforts to make people aware of what they are doing and most importantly making it in a quite fun way!
Ivana and Guillermo, thank you guys for being my paranymphs during my defense and for all your support in this period. People in Otto group; spending more than four years with you is truly an unforgettable period in my life. Andrea, the first months in Groningen was memorable especially when people insistently thought I was you! :) Asish and Morteza, thank you guys for your initiations in projects which eventually turned to be a big part of my research. Ivica, I am really glad to share my office with you and will really miss our non-scientific discussions in the office. Giulia, Boris, Gael, Saleh, Elio, Shuo, Jim, Andreas, Xiaoming, Jim, Bin, Soma, David, Babis, thank you all guys for all the time that we spent together. And all the new members of Otto group, I wish you good luck and a big success in your studies.
Of course, dear Turkish crew, Burcu, Pınar ve Se¸ckin, Ay¸seg¨ul, Turhan, Arman, Veclal abla thank you for all your company. M¨uge & Patrick, I’m so glad to know you guys. I will always appreciate our talks that helped me to survive PhD life. And Billur, we are the best examples to show long distances can bring people closer ;)
And one day, we will make it!
Yi˘git, we have started our journey by building a life abroad and have grown up together. Thank you for being my best friend and my life-long partner. And thank you for always believing in me more than I do myself.
Hayattaki en b¨uy¨uk ¸sansım ailem, uzak mesafelerde bile olsak elinizi ¨uzerimden hi¸c ¸cekmediniz ve ¸cekmeyeceksiniz, biliyorum. Aldı˘gım her kararı destekledi˘giniz ve her zaman yanımda oldu˘gunuz i¸cin te¸sekk¨ur ederim. ˙Iyi ki varsınız.
Meniz Altay
email: meniztezcan@gmail.com orcid id: 0000-0003-1225-3104
September 2019 Doctor of Philosophy in Chemistry University of Groningen, Groningen Supervisor: Prof. Sijbren Otto
September 2013 Master of Science in Chemistry
Middle East Techical University, Ankara, Turkey Supervisor: Prof. Salih ¨Ozc¸ubukc¸u
June 2011 Bachelor of Science in Chemistry
Middle East Techical University, Ankara, Turkey Spring 2010 Summer Internship
Ghent University, Ghent, Belgium Supervisor: Prof. Matthias D’hooghe
List of Publications
1. Y. Altay, M. Altay, J. Ottele, P. W. J. M. Frederix, M. Malakoutikhah, G. Leonetti and S. Otto, “A Structural Survey in the Search for Novel Self-Replicating Peptides”, Manuscript in preparation.
2. X. Miao, N. Eisink, P. Nowak, M. Altay, G. Leonetti, I. Maric, M. Witte, S. Otto, “Development of Stable Iron Oxide Nanoparticles for Facile Surface Functionalization”, Manuscript submitted.
And one day, we will make it!
Yi˘git, we have started our journey by building a life abroad and have grown up together. Thank you for being my best friend and my life-long partner. And thank you for always believing in me more than I do myself.
Hayattaki en b¨uy¨uk ¸sansım ailem, uzak mesafelerde bile olsak elinizi ¨uzerimden hi¸c ¸cekmediniz ve ¸cekmeyeceksiniz, biliyorum. Aldı˘gım her kararı destekledi˘giniz ve her zaman yanımda oldu˘gunuz i¸cin te¸sekk¨ur ederim. ˙Iyi ki varsınız.
Meniz Altay
email: meniztezcan@gmail.com orcid id: 0000-0003-1225-3104
September 2019 Doctor of Philosophy in Chemistry University of Groningen, Groningen Supervisor: Prof. Sijbren Otto
September 2013 Master of Science in Chemistry
Middle East Techical University, Ankara, Turkey Supervisor: Prof. Salih ¨Ozc¸ubukc¸u
June 2011 Bachelor of Science in Chemistry
Middle East Techical University, Ankara, Turkey Spring 2010 Summer Internship
Ghent University, Ghent, Belgium Supervisor: Prof. Matthias D’hooghe
List of Publications
1. Y. Altay, M. Altay, J. Ottele, P. W. J. M. Frederix, M. Malakoutikhah, G. Leonetti and S. Otto, “A Structural Survey in the Search for Novel Self-Replicating Peptides”, Manuscript in preparation.
2. X. Miao, N. Eisink, P. Nowak, M. Altay, G. Leonetti, I. Maric, M. Witte, S. Otto, “Development of Stable Iron Oxide Nanoparticles for Facile Surface Functionalization”, Manuscript submitted.
3. B. Bartolec, G. Leonetti, J. Li, W. Smit, M. Altay, G. M. Santiago, Y. Yan, S. Otto, “Emergence of Compartments formed from Unconventional Surfactants in Dynamic Combinatorial Libraries”, Manuscript submitted.
4. B. Bartolec, M. Altay, S. Otto, “Template-promoted self-replication in dy-namic combinatorial libraries made from a simple building block”, Chem. Comm. 2018, 54, 13096-13098
5. Y. Altay, M. Altay and S. Otto, “Existing Self-Replicators Can Direct the Emergence of New Ones”, Chem. Eur. J. 2018, 24, 11911 - 11915.
6. M. Altay, Y. Altay and S.Otto, “Parasitic Behavior of Self-Replicating Molecules”, Angew. Chem. Int. Ed., 2018, 139 (57), 10564 - 10568.
7. Y. Altay, M. Tezcan and S. Otto, “Emergence of a New Self-Replicator from a Dynamic Combinatorial Library Requires a Specific Pre-Existing Replicator”, J. Am. Chem. Soc., 2017, 139 (39), 13612 - 13615.
8. D. Komaromy, M. Tezcan, G. Schaeffer, I. Maric, S. Otto. “Effector-Triggered Self-Replication in Coupled Subsystems”, Angew. Chem. Int. Ed. 2017, 56, 14658-14662.
9. D. Komaromy, M. C. A. Stuart, G. M. Santiago, M. Tezcan, V. V. Krasnikov, S. Otto, “Self-Assembly Can Direct Dynamic Covalent Bond Formation toward Diversity or Specificity”, J. Am. Chem. Soc. 2017, 139, 6234-6241. 10. A. Pal, M. Malakoutikhah, G. Leonetti, M. Tezcan, M. Colomb-Delsuc, V.
D. Nguyen, J. van der Gucht, S. Otto, “Controlling the Structure and Length of Self-Synthesizing Supramolecular Polymers through Nucleated Growth and Disassembly”, Angew. Chem. Int. Ed. 2015, 54, 7852-7856.
11. S. Stankovic, H. Goossens, S. Catak, M. Tezcan, M. Waroquier, V. van Spey-broeck, M. D’hooghe, and N. de Kimpe, “Solvent-Controlled Selective Trans-formation of 2-Bromomethyl-2- methylaziridines to Functionalized Aziridines and Azetidines”, J. Org. Chem. 2012, 77, 3181-3190.
3. B. Bartolec, G. Leonetti, J. Li, W. Smit, M. Altay, G. M. Santiago, Y. Yan, S. Otto, “Emergence of Compartments formed from Unconventional Surfactants in Dynamic Combinatorial Libraries”, Manuscript submitted.
4. B. Bartolec, M. Altay, S. Otto, “Template-promoted self-replication in dy-namic combinatorial libraries made from a simple building block”, Chem. Comm. 2018, 54, 13096-13098
5. Y. Altay, M. Altay and S. Otto, “Existing Self-Replicators Can Direct the Emergence of New Ones”, Chem. Eur. J. 2018, 24, 11911 - 11915.
6. M. Altay, Y. Altay and S.Otto, “Parasitic Behavior of Self-Replicating Molecules”, Angew. Chem. Int. Ed., 2018, 139 (57), 10564 - 10568.
7. Y. Altay, M. Tezcan and S. Otto, “Emergence of a New Self-Replicator from a Dynamic Combinatorial Library Requires a Specific Pre-Existing Replicator”, J. Am. Chem. Soc., 2017, 139 (39), 13612 - 13615.
8. D. Komaromy, M. Tezcan, G. Schaeffer, I. Maric, S. Otto. “Effector-Triggered Self-Replication in Coupled Subsystems”, Angew. Chem. Int. Ed. 2017, 56, 14658-14662.
9. D. Komaromy, M. C. A. Stuart, G. M. Santiago, M. Tezcan, V. V. Krasnikov, S. Otto, “Self-Assembly Can Direct Dynamic Covalent Bond Formation toward Diversity or Specificity”, J. Am. Chem. Soc. 2017, 139, 6234-6241. 10. A. Pal, M. Malakoutikhah, G. Leonetti, M. Tezcan, M. Colomb-Delsuc, V.
D. Nguyen, J. van der Gucht, S. Otto, “Controlling the Structure and Length of Self-Synthesizing Supramolecular Polymers through Nucleated Growth and Disassembly”, Angew. Chem. Int. Ed. 2015, 54, 7852-7856.
11. S. Stankovic, H. Goossens, S. Catak, M. Tezcan, M. Waroquier, V. van Spey-broeck, M. D’hooghe, and N. de Kimpe, “Solvent-Controlled Selective Trans-formation of 2-Bromomethyl-2- methylaziridines to Functionalized Aziridines and Azetidines”, J. Org. Chem. 2012, 77, 3181-3190.
