Calix[6]arènes présentant une chiralité inhérente

Inherent chiralty, which arises from a concave structure associated with asymetric substitution, is the most common form of chiralty and is fundamental in enzymatic recognition : although aminoacids have an asymetric center, the folding of proteins creates the inherently chiral active site of enzymes and is responsible for the extraordinary selectivity of enzymatic reactions. Calix[6]arenes have been used as a tool to study complex enzymatic processes. They have also been used to build artificial molecular receptors for cations, anions or neutral molecules through very specific interactions. The goal of this thesis is the synthesis of inherently chiral calix[6]arenes by introducing different functionalities devoid of asymetric centers, and the study of the recognition of chiral molecules. First, we developped a biomimetic and supramolecular strategy to monofunctionalize a zinc calix[6]arene complex bearin three imidazole arms or a tris(2-aminoethyl)amine cap, with high selectivity. By using the recognition abilities of theses substrates, several molecules were liked only one of the three equivalent sites of the big rim of the calixarene. The limits of the biomimetic « monoclick » reaction were also quantified. The monofunctionalized complexes are new objects whose abilities as molecular receptors greatly differ from the previous « funnel complexes » described by our team. The control of the access of the cavity of Zn(II), Cu(II) and Cu(I) complexes to exogenous ligands was thoroughly studied with different competitive ligands. Also, we proved that the access to the cavity could be controled with an electrochemical switch. We also developed strategies to synthesize inherently chiral calix[6]arenes from monofunctionalized complexes and we synthesized the first inherently chiral funnel complex. Its chirality was evidenced by the inclusion of chiral and achiral guests. We also provided the proof of concept that these particular phenomena could be simply studied with 19F NMR spectroscopy.La chiralité inhérente, provenant d’une structure concave associée à une substitution dissymétrique, est la forme de chiralité la plus répandue et est une des bases fondamentales de la reconnaissance enzymatique : outre le fait que les briques constitutives des protéines présentent un carbone asymétrique, leur repliement définit la chiralité inhérente de la poche du site actif, et est responsable de l’étonnante sélectivité des réactions enzymatiques. De façon générale, les calixarènes ont été notamment utilisés afin de modéliser les processus enzymatiques complexes. Ils sont ainsi à la base de la construction de nombreux récepteurs moléculaires artificiels, capables de reconnaître des cations, des anions ou des molécules neutres par des interactions spécifiques. L’objectif de cette thèse est la synthèse de calix[6]arènes présentant une chiralité inhérente, en leur introduisant différentes fonctionnalités différentes en l’absence de carbone asymétrique, ainsi que l’étude de leurs propriétés de reconnaissance de molécules chirales. Cet objectif est indissociable du challenge classique de la chimie organique qu’est la monofonctionnalisation de molécules possédant plusieurs fonctions réactives équivalentes. Dans un premier temps, nous avons utilisé une stratégie biomimétique et supramoléculaire pour monofonctionnaliser très sélectivement un complexe zincique de calix[6]arène portant trois bras imidazole ou un chapeau Tris(2-aminoÉthyl)AmiNe. En tirant profit de la nature réceptrice de ces complexes, différents substrats ont pu être greffés à la structure sur un seul des trois sites équivalents du grand col. Les limites de cette réaction « monoclick » biomimétique ont été quantifiées. Les complexes monofonctionnalisés sont de nouveaux objets aux propriétés réceptrices considérablement différentes des « complexes entonnoirs » décrits par notre équipe. Le contrôle de l’accès de la cavité des complexes de Zn(II), Cu(I) et Cu(II) pour des ligands exogènes a été étudiés en présence de différents ligands compétiteurs. Par ailleurs, nous avons montré que dans le cas des complexes de cuivre, l’accès à la cavité pouvait être contrôlé par un switch électrochimique. Nous avons également développé deux stratégies de synthèse de calix[6]arènes chiraux de façon inhérente à partir de précurseurs monofonctionnalisés, et nous avons synthétisé le premier »complexe entonnoir » présentant cette propriété. Sa chiralité a été mise en évidence par l’inclusion de ligands achiraux et achiraux. Nous avons également prouvé que ces phénomènes complexes pouvaient être étudiés simplement grâce à la technique RMN 19F

Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

SummaryThe deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR

A circumplanetary disk around PDS70c

Funding: This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 101002188 and No. 832428). J.B. acknowledges support by NASA through the NASA Hubble Fellowship grant #HST-HF2-51427.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Incorporated, under NASA contract NAS5-26555. S.F. acknowledges an ESO Fellowship. S.A. acknowledges support from the National Aeronautics and Space Administration under grant No. 17-XRP17 2-0012 issued through the Exoplanets Research Program. A.I. acknowledges support from the National Science Foundation under grant No. AST1715719 and from NASA under grant No. 80NSSC18K0828. J.M.C. acknowledges support from the National Aeronautics and Space Administration under grant No. 15XRP15_20140 issued through the Exoplanets Research Program. N.T.K. and P.P. acknowledge support provided by the Alexander von Humboldt Foundation in the framework of the Sofja Kovalevskaja Award endowed by the Federal Ministry of Education and Research.PDS 70 is a unique system in which two protoplanets, PDS 70 b and c, have been discovered within the dust-depleted cavity of their disk, at ~22 and 34 au, respectively, by direct imaging at infrared wavelengths. Subsequent detection of the planets in the Hα line indicates that they are still accreting material through circumplanetary disks. In this Letter, we present new Atacama Large Millimeter/submillimeter Array (ALMA) observations of the dust continuum emission at 855 μm at high angular resolution (~20 mas, 2.3 au) that aim to resolve the circumplanetary disks and constrain their dust masses. Our observations confirm the presence of a compact source of emission co-located with PDS 70 c, spatially separated from the circumstellar disk and less extended than ~1.2 au in radius, a value close to the expected truncation radius of the circumplanetary disk at a third of the Hill radius. The emission around PDS 70 c has a peak intensity of ~86 ± 16 μJy beam-1, which corresponds to a dust mass of ~0.031 M⊕ or ~0.007 M⊕, assuming that it is only constituted of 1 μm or 1 mm sized grains, respectively. We also detect extended, low surface brightness continuum emission within the cavity near PDS 70 b. We observe an optically thin inner disk within 18 au of the star with an emission that could result from small micron-sized grains transported from the outer disk through the orbits of b and c. In addition, we find that the outer disk resolves into a narrow and bright ring with a faint inner shoulder.Publisher PDFPeer reviewe

MicroRNA signatures in vitreous humour and plasma of patients with exudative AMD

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide affecting individuals over the age of 50. The neovascular form (NV AMD) is characterized by choroidal neovascularization (CNV) and responsible for the majority of central vision impairment. Using non-biased microRNA arrays and individual TaqMan qPCRs, we profiled miRNAs in the vitreous humour and plasma of patients with NV AMD. We identified a disease-associated increase in miR-146a and a decrease in miR-106b and miR-152 in the vitreous humour which was reproducible in plasma. Moreover, miR-146a/miR-106b ratios discriminated patients with NV AMD with an area under the Receiver Operating Characteristic curve (ROC AUC) of 0,977 in vitreous humour and 0,915 in plasma suggesting potential for a blood-based diagnostic. Furthermore, using the AMD Gene Consortium (AGC) we mapped a NV AMD-associated SNP (rs1063320) in a binding site for miR-152-3p in the HLA-G gene. The relationship between our detected miRNAs and NV AMD related genes was also investigated using gene sets derived from the Ingenuity Pathway Analysis (IPA). To our knowledge, our study is the first to correlate vitreal and plasma miRNA signatures with NV AMD, highlighting potential future worth as biomarkers and providing insight on NV AMD pathogenesis

Trueness and precision of the real-time RT-PCR method for quantifying the chronic bee paralysis virus genome in bee homogenates evaluated by a comparative inter-laboratory study

The Chronic bee paralysis virus (CBPV) is the aetiological agent of chronic bee paralysis, a contagious disease associated with nervous disorders in adult honeybees leading to massive mortalities in front of the hives. Some of the clinical signs frequently reported, such as trembling, may be confused with intoxication syndromes. Therefore, laboratory diagnosis using real-time PCR to quantify CBPV loads is used to confirm disease. Clinical signs of chronic paralysis are usually associated with viral loads higher than 108 copies of CBPV genome copies per bee (8 log(10) CBPV/bee). This threshold is used by the European Union Reference Laboratory for Bee Health to diagnose the disease. In 2015, the accuracy of measurements of three CBPV loads (5, 8 and 9 log(10) CBPV/bee) was assessed through an inter-laboratory study. Twenty-one participants, including 16 European National Reference Laboratories, received 13 homogenates of CBPV-infected bees adjusted to the three loads. Participants were requested to use the method usually employed for routine diagnosis. The quantitative results (n = 270) were analysed according to international standards NF ISO 13528 (2015) and NF ISO 5725-2 (1994). The standard deviations of measurement reproducibility (S-R) were 0.83, 1.06 and 1.16 at viral loads 5, 8 and 9 log(10) CBPV/bee, respectively. The inter-laboratory confidence of viral quantification (+/- 1.96 S-R) at the diagnostic threshold (8 log(10) CBPV/bee) was +/- 2.08 log(10) CBPV/bee. These results highlight the need to take into account the confidence of measurements in epidemiological studies using results from different laboratories. Considering this confidence, viral loads over 6 log(10) CBPV/bee may be considered to indicate probable cases of chronic paralysis

Margarita de Sossa, Sixteenth-Century Puebla de los Ángeles, New Spain (Mexico)

Margarita de Sossa’s freedom journey was defiant and entrepreneurial. In her early twenties, still enslaved in Portugal, she took possession of her body; after refusing to endure her owner’s sexual demands, he sold her, and she was transported to Mexico. There, she purchased her freedom with money earned as a healer and then conducted an enviable business as an innkeeper. Sossa’s biography provides striking insights into how she conceptualized freedom in terms that included – but was not limited to – legal manumission. Her transatlantic biography offers a rare insight into the life of a free black woman (and former slave) in late sixteenth-century Puebla, who sought to establish various degrees of freedom for herself. Whether she was refusing to acquiesce to an abusive owner, embracing entrepreneurship, marrying, purchasing her own slave property, or later using the courts to petition for divorce. Sossa continued to advocate on her own behalf. Her biography shows that obtaining legal manumission was not always equivalent to independence and autonomy, particularly if married to an abusive husband, or if financial successes inspired the envy of neighbors

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR

Relationship of edge localized mode burst times with divertor flux loop signal phase in JET

A phase relationship is identified between sequential edge localized modes (ELMs) occurrence times in a set of H-mode tokamak plasmas to the voltage measured in full flux azimuthal loops in the divertor region. We focus on plasmas in the Joint European Torus where a steady H-mode is sustained over several seconds, during which ELMs are observed in the Be II emission at the divertor. The ELMs analysed arise from intrinsic ELMing, in that there is no deliberate intent to control the ELMing process by external means. We use ELM timings derived from the Be II signal to perform direct time domain analysis of the full flux loop VLD2 and VLD3 signals, which provide a high cadence global measurement proportional to the voltage induced by changes in poloidal magnetic flux. Specifically, we examine how the time interval between pairs of successive ELMs is linked to the time-evolving phase of the full flux loop signals. Each ELM produces a clear early pulse in the full flux loop signals, whose peak time is used to condition our analysis. The arrival time of the following ELM, relative to this pulse, is found to fall into one of two categories: (i) prompt ELMs, which are directly paced by the initial response seen in the flux loop signals; and (ii) all other ELMs, which occur after the initial response of the full flux loop signals has decayed in amplitude. The times at which ELMs in category (ii) occur, relative to the first ELM of the pair, are clustered at times when the instantaneous phase of the full flux loop signal is close to its value at the time of the first ELM

NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods

Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submit- Avenue, Silver Spring, Maryland 20993; 22Glycoscience Research Laboratory, Genos, Borongajska cesta 83h, 10 000 Zagreb, Croatia; 23Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacˇ ic´ a 1, 10 000 Zagreb, Croatia; 24Department of Chemistry, Georgia State University, 100 Piedmont Avenue, Atlanta, Georgia 30303; 25glyXera GmbH, Brenneckestrasse 20 * ZENIT / 39120 Magdeburg, Germany; 26Health Products and Foods Branch, Health Canada, AL 2201E, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9 Canada; 27Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama Higashi-Hiroshima 739–8530 Japan; 28ImmunoGen, 830 Winter Street, Waltham, Massachusetts 02451; 29Department of Medical Physiology, Jagiellonian University Medical College, ul. Michalowskiego 12, 31–126 Krakow, Poland; 30Department of Pathology, Johns Hopkins University, 400 N. Broadway Street Baltimore, Maryland 21287; 31Mass Spec Core Facility, KBI Biopharma, 1101 Hamlin Road Durham, North Carolina 27704; 32Division of Mass Spectrometry, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongwon-gu, Cheongju Chungbuk, 363–883 Korea (South); 33Advanced Therapy Products Research Division, Korea National Institute of Food and Drug Safety, 187 Osongsaengmyeong 2-ro Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 363–700, Korea (South); 34Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; 35Ludger Limited, Culham Science Centre, Abingdon, Oxfordshire, OX14 3EB, United Kingdom; 36Biomolecular Discovery and Design Research Centre and ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, North Ryde, Australia; 37Proteomics, Central European Institute for Technology, Masaryk University, Kamenice 5, A26, 625 00 BRNO, Czech Republic; 38Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany; 39Department of Biomolecular Sciences, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany; 40AstraZeneca, Granta Park, Cambridgeshire, CB21 6GH United Kingdom; 41Merck, 2015 Galloping Hill Rd, Kenilworth, New Jersey 07033; 42Analytical R&D, MilliporeSigma, 2909 Laclede Ave. St. Louis, Missouri 63103; 43MS Bioworks, LLC, 3950 Varsity Drive Ann Arbor, Michigan 48108; 44MSD, Molenstraat 110, 5342 CC Oss, The Netherlands; 45Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5–1 Higashiyama, Myodaiji, Okazaki 444–8787 Japan; 46Graduate School of Pharmaceutical Sciences, Nagoya City University, 3–1 Tanabe-dori, Mizuhoku, Nagoya 467–8603 Japan; 47Medical & Biological Laboratories Co., Ltd, 2-22-8 Chikusa, Chikusa-ku, Nagoya 464–0858 Japan; 48National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG United Kingdom; 49Division of Biological Chemistry & Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158–8501 Japan; 50New England Biolabs, Inc., 240 County Road, Ipswich, Massachusetts 01938; 51New York University, 100 Washington Square East New York City, New York 10003; 52Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, United Kingdom; 53GlycoScience Group, The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland; 54Department of Chemistry, North Carolina State University, 2620 Yarborough Drive Raleigh, North Carolina 27695; 55Pantheon, 201 College Road East Princeton, New Jersey 08540; 56Pfizer Inc., 1 Burtt Road Andover, Massachusetts 01810; 57Proteodynamics, ZI La Varenne 20–22 rue Henri et Gilberte Goudier 63200 RIOM, France; 58ProZyme, Inc., 3832 Bay Center Place Hayward, California 94545; 59Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho Nakagyo-ku, Kyoto, 604 8511 Japan; 60Children’s GMP LLC, St. Jude Children’s Research Hospital, 262 Danny Thomas Place Memphis, Tennessee 38105; 61Sumitomo Bakelite Co., Ltd., 1–5 Muromati 1-Chome, Nishiku, Kobe, 651–2241 Japan; 62Synthon Biopharmaceuticals, Microweg 22 P.O. Box 7071, 6503 GN Nijmegen, The Netherlands; 63Takeda Pharmaceuticals International Co., 40 Landsdowne Street Cambridge, Massachusetts 02139; 64Department of Chemistry and Biochemistry, Texas Tech University, 2500 Broadway, Lubbock, Texas 79409; 65Thermo Fisher Scientific, 1214 Oakmead Parkway Sunnyvale, California 94085; 66United States Pharmacopeia India Pvt. Ltd. IKP Knowledge Park, Genome Valley, Shamirpet, Turkapally Village, Medchal District, Hyderabad 500 101 Telangana, India; 67Alberta Glycomics Centre, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 68Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 69Department of Chemistry, University of California, One Shields Ave, Davis, California 95616; 70Horva´ th Csaba Memorial Laboratory for Bioseparation Sciences, Research Center for Molecular Medicine, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Egyetem ter 1, Hungary; 71Translational Glycomics Research Group, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprem, Egyetem ut 10, Hungary; 72Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way Newark, Delaware 19711; 73Proteomics Core Facility, University of Gothenburg, Medicinaregatan 1G SE 41390 Gothenburg, Sweden; 74Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Institute of Biomedicine, Sahlgrenska Academy, Medicinaregatan 9A, Box 440, 405 30, Gothenburg, Sweden; 75Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Bruna Straket 16, 41345 Gothenburg, Sweden; 76Department of Chemistry, University of Hamburg, Martin Luther King Pl. 6 20146 Hamburg, Germany; 77Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2; 78Laboratory of Mass Spectrometry of Interactions and Systems, University of Strasbourg, UMR Unistra-CNRS 7140, France; 79Natural and Medical Sciences Institute, University of Tu¨ bingen, Markwiesenstrae 55, 72770 Reutlingen, Germany; 80Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; 81Division of Bioanalytical Chemistry, Amsterdam Institute for Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; 82Department of Chemistry, Waters Corporation, 34 Maple Street Milford, Massachusetts 01757; 83Zoetis, 333 Portage St. Kalamazoo, Michigan 49007 Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. Received July 24, 2019, and in revised form, August 26, 2019 Published, MCP Papers in Press, October 7, 2019, DOI 10.1074/mcp.RA119.001677 ER: NISTmAb Glycosylation Interlaboratory Study 12 Molecular & Cellular Proteomics 19.1 Downloaded from https://www.mcponline.org by guest on January 20, 2020 ted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide communityderived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Molecular & Cellular Proteomics 19: 11–30, 2020. DOI: 10.1074/mcp.RA119.001677.L

Calix[6]arenes with inherent chirality

La chiralité inhérente, provenant d’une structure concave associée à une substitution dissymétrique, est la forme de chiralité la plus répandue et est une des bases fondamentales de la reconnaissance enzymatique : outre le fait que les briques constitutives des protéines présentent un carbone asymétrique, leur repliement définit la chiralité inhérente de la poche du site actif, et est responsable de l’étonnante sélectivité des réactions enzymatiques. De façon générale, les calixarènes ont été notamment utilisés afin de modéliser les processus enzymatiques complexes. Ils sont ainsi à la base de la construction de nombreux récepteurs moléculaires artificiels, capables de reconnaître des cations, des anions ou des molécules neutres par des interactions spécifiques. L’objectif de cette thèse est la synthèse de calix[6]arènes présentant une chiralité inhérente, en leur introduisant différentes fonctionnalités différentes en l’absence de carbone asymétrique, ainsi que l’étude de leurs propriétés de reconnaissance de molécules chirales. Cet objectif est indissociable du challenge classique de la chimie organique qu’est la monofonctionnalisation de molécules possédant plusieurs fonctions réactives équivalentes. Dans un premier temps, nous avons utilisé une stratégie biomimétique et supramoléculaire pour monofonctionnaliser très sélectivement un complexe zincique de calix[6]arène portant trois bras imidazole ou un chapeau Tris(2-aminoÉthyl)AmiNe. En tirant profit de la nature réceptrice de ces complexes, différents substrats ont pu être greffés à la structure sur un seul des trois sites équivalents du grand col. Les limites de cette réaction « monoclick » biomimétique ont été quantifiées. Les complexes monofonctionnalisés sont de nouveaux objets aux propriétés réceptrices considérablement différentes des « complexes entonnoirs » décrits par notre équipe. Le contrôle de l’accès de la cavité des complexes de Zn(II), Cu(I) et Cu(II) pour des ligands exogènes a été étudiés en présence de différents ligands compétiteurs. Par ailleurs, nous avons montré que dans le cas des complexes de cuivre, l’accès à la cavité pouvait être contrôlé par un switch électrochimique. Nous avons également développé deux stratégies de synthèse de calix[6]arènes chiraux de façon inhérente à partir de précurseurs monofonctionnalisés, et nous avons synthétisé le premier »complexe entonnoir » présentant cette propriété. Sa chiralité a été mise en évidence par l’inclusion de ligands achiraux et achiraux. Nous avons également prouvé que ces phénomènes complexes pouvaient être étudiés simplement grâce à la technique RMN 19F.Inherent chiralty, which arises from a concave structure associated with asymetric substitution, is the most common form of chiralty and is fundamental in enzymatic recognition : although aminoacids have an asymetric center, the folding of proteins creates the inherently chiral active site of enzymes and is responsible for the extraordinary selectivity of enzymatic reactions. Calix[6]arenes have been used as a tool to study complex enzymatic processes. They have also been used to build artificial molecular receptors for cations, anions or neutral molecules through very specific interactions. The goal of this thesis is the synthesis of inherently chiral calix[6]arenes by introducing different functionalities devoid of asymetric centers, and the study of the recognition of chiral molecules. First, we developped a biomimetic and supramolecular strategy to monofunctionalize a zinc calix[6]arene complex bearin three imidazole arms or a tris(2-aminoethyl)amine cap, with high selectivity. By using the recognition abilities of theses substrates, several molecules were liked only one of the three equivalent sites of the big rim of the calixarene. The limits of the biomimetic « monoclick » reaction were also quantified. The monofunctionalized complexes are new objects whose abilities as molecular receptors greatly differ from the previous « funnel complexes » described by our team. The control of the access of the cavity of Zn(II), Cu(II) and Cu(I) complexes to exogenous ligands was thoroughly studied with different competitive ligands. Also, we proved that the access to the cavity could be controled with an electrochemical switch. We also developed strategies to synthesize inherently chiral calix[6]arenes from monofunctionalized complexes and we synthesized the first inherently chiral funnel complex. Its chirality was evidenced by the inclusion of chiral and achiral guests. We also provided the proof of concept that these particular phenomena could be simply studied with 19F NMR spectroscopy