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A Plausible Prebiotic Synthesis of Thiol-Rich Peptides: the Reaction of Aminothiols with Aminonitriles

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A Plausible Prebiotic Synthesis of Thiol-Rich Peptides: the Reaction of Aminothiols with Aminonitriles A plausible prebiotic synthesis of thiol-rich peptides : the reaction of aminothiols with aminonitriles Ibrahim Shalayel To cite this version: Ibrahim Shalayel. A plausible prebiotic synthesis of thiol-rich peptides : the reaction of aminoth- iols with aminonitriles. Organic chemistry. Université Grenoble Alpes, 2018. English. NNT : 2018GREAV055. tel-02131562 HAL Id: tel-02131562 https://tel.archives-ouvertes.fr/tel-02131562 Submitted on 16 May 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE Pour obtenir le grade de DOCTEUR DE LA COMMUNAUTÉ UNIVERSITÉ GRENOBLE ALPES Spécialité : Chimie organique Arrêté ministériel : 25 mai 2016 Présentée par Ibrahim SHALAYEL Thèse dirigée par Yannick VALLEE, UGA préparée au sein du Laboratoire Département de Chimie Moléculaire dans l'École Doctorale Chimie et Sciences du Vivant Synthèse prébiotique plausible de peptides riches en thiol : la réaction des aminothiols avec les aminonitriles A plausible prebiotic synthesis of thiol-rich peptides: the reaction of aminothiols with aminonitriles Thèse soutenue publiquement le 17 décembre 2018, devant le jury composé de : Monsieur YANNICK VALLEE PROFESSEUR, UNIVERSITE GRENOBLE ALPES, Directeur de thèse Madame MARTINE DEMEUNYNCK DIRECTRICE DE RECHERCHE, CNRS DELEGATION ALPES, Président Monsieur JEAN-CLAUDE GUILLEMIN DIRECTEUR DE RECHERCHE, CNRS DELEGATION BRETAGNE PAYS DE LOIRE, Rapporteur Monsieur STEPHANE PERRIO MAITRE DE CONFERENCES, UNIVERSITE DE CAEN NORMANDIE, Rapporteur Dedicated to my beloved angel, Azadeh ACKNOWLEDGMENTS In the first place, I would like to thank my supervisor, Prof. Yannick VALLÉE for his enormous support and for his very kind personality. This work would not have been possible without his advice, guidance and brilliant ideas. I am very grateful to my thesis committee: Prof. Martine DEMEUNYNCK, Prof. Jean- Claude GUILLEMIN and Prof. Stephane PERRIO for their time and their valuable comments and remarks on the manuscript. I would also like to thank Dr. Maxime BRIDOUX who was unfortunately not able to attend the defence. I would like to acknowledge the “Consulat Général de France à Jérusalem”, Campus France and the “mairie de Gières” for the financial support of my thesis. Special thanks to George MORIN, Anne-Marie, Gilles and “L’association Gieres-Palestine” for their continuous help. I would like to thank in a very special way Frederic MINASSIAN who helped me in every possible way to handle the difficulties I faced at the beginning of my master. It was not possible for me to keep going without his help. I would like to extend my thanks to Damien JOUVENOT and Rajaa FARRAN with whom I had my first internship in France. I am so grateful to Prof. Yves GIMBERT and Prof. Jean-Luc DECOUT for their valuable comments throughout the review of my CSI reports. Many thanks go to Anne MILET and Maxime BRIDOUX for the nice corporation in our research. I should also thank Rodolphe GUÉRET, Laure FORT and Amelie DURAND for the time taken to analyse my samples. I cannot let this opportunity pass without expressing my deep gratitude to my friends and colleagues in SeRCO team: Prof. Jean-Francoise POISSON (the director of our team), Sebastien, Bernard, Pierre-Yves (who was always ready to give a helping hand), Sandrine, Alice, Veronique, Florian, Pascale, Martine, Jerome, David, Pierre-Marc, Nathalie, Mathieu and Benjamin. Many thanks to Jean Michel, Carlos, Pierre, Beatrice, Christian, Nicolas, Caroline, and all nice people in the DCM. Great thanks go to my friends in the lab with whom I shared nice moments and had hundreds of coffee breaks: Aladdin (le prince), Wathiq, Vianney, Evelyn, Laura and Ali (who designed my citation style on Mendeley). Many thanks to Salia (Le Roi), Anais (La fleure) and Thi (le soleil) for all wonderful moments and for making my stay enjoyable. I wish the best luck for Naoual (la princesses), Sparta, and Seydou in their PhD journey with Yannick. Thanks to everyone who participated in the project and shared the fume hoods with me: Ragha, Kieu-Dung, Audrey, Vnghia, Sarah, Alicia, Rudy, Filip, Bilel, Nicolas and Marielle. I can never forget Edgar; it is true that we miss him but he will be always in our thoughts. I cannot forget to express my deep sense of gratitude to Erin, Jane, Alison, Roy, Ahmed and all my amazing colleagues in the English department at DLST. Last but not least, I’m sincerely grateful to my beloved family in Palestine and to all my friends, especially Ali (le president) who was also my neighbour for 5 years in Gieres. Table of contents Table of Contents Introduction ........................................................................................................................................... 5 A. A brief history of evolution ...................................................................................................... 5 B. Conditions on Earth 4 billion years ago ................................................................................ 10 C. What molecules could come from space?.............................................................................. 13 D. Synthesis of the “molecular bricks” of life on Earth ........................................................... 17 E. Prebiotic synthesis of peptides ............................................................................................... 23 F. Today’s role of thiols in biology ............................................................................................. 30 Chapter I: Prebiotic formation of thiol containing dipeptides from aminonitriles and aminothiols........................................................................................................................................... 39 I.1 Introduction ............................................................................................................................ 39 I.2 Synthesis of aminonitriles ...................................................................................................... 40 I.2.1 Synthesis of racemic α-aminonitriles ............................................................................. 40 I.2.2 Synthesis of L-aminonitriles ........................................................................................... 40 I.2.2 Synthesis of (S)-2-amino-1,4-butanedinitrile 32 ........................................................... 45 I.2.3 Synthesis of 2-amino-4-cyanobutanoic acid 35 ............................................................. 46 I.2.4 Synthesis of (S)-2-aminopentanedinitrile 38 ................................................................. 47 I.2.6 Synthesis of Gly-Gly-CN 42 ............................................................................................ 48 I.2.7 Synthesis of Gly-Gly-Gly-CN 45 .................................................................................... 48 I.3 Reactions between aminonitriles and aminothiols .............................................................. 49 I.3.1 Reaction of aminoacetonitrile with cysteine .................................................................. 49 I.3.2 Reaction of aminoacetonitrile with homocysteine ........................................................ 53 I.3.3 Reaction of alpha substituted aminonitriles with cysteine and homocysteine ........... 55 I.3.4 N-Acetyl aminoacetonitrile with cysteine ...................................................................... 57 I.3.5 Reaction of β-aminopropionitrile with cysteine and homocysteine ............................ 58 I.3.6 Competition between α and β-aminonitrile ................................................................... 60 I.3.6.a Competition between α and β-aminonitrile with cysteine ......................................... 60 I.3.6.b Competition between α and β-aminonitrile with homocysteine ............................... 61 I.3.7 Reaction with 2-amino-1,4-butanedinitrile ................................................................... 61 I.4 Formation of Tri and Tetra-peptides ................................................................................... 62 I.4.1 Reaction of cysteine with GlyGly-CN and GlyGlyGly-CN .......................................... 62 I.4.2 Reaction of aminoacetonitrile with Cys-Gly ................................................................. 63 I.4.3 Competition between cysteine and Cys-Gly .................................................................. 64 Table of contents I.5 Reactions with cysteine amide ............................................................................................... 65 I.5.1 Reaction of cysteine amide with aminoacetonitrile ...................................................... 66 I.5.2 Reaction of cysteine amide with aminoacetonitrile ...................................................... 67 I.6 Reaction of aminoacetonitrile with cysteamine ................................................................... 69 I.7 Reaction with penicillamine................................................................................................... 70
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