Institut de Chimie et Biochimie Moléculaires et Supramoléculaires

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAryl−Aryl Bond Formation One Century after the Discovery of the Ullmann ReactionJwanro Hassan, Marc Sévignon, Christel Gozzi, Emmanuelle Schulz, and Marc LemaireView Author Information Laboratoire de Catalyse et Synthèse Organique, UMR 5622, Université Claude Bernard Lyon 1, CPE, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France, and Laboratoire de Catalyse Moleculaire, UPRESA, CNRS 8075, Institut de Chimie Moléculaire d'Orsay, Université Paris-Sud, 91405 Orsay Cedex, France Cite this: Chem. Rev. 2002, 102, 5, 1359–1470Publication Date (Web):March 8, 2002Publication History Received9 July 2001Published online8 March 2002Published inissue 1 May 2002https://pubs.acs.org/doi/10.1021/cr000664rhttps://doi.org/10.1021/cr000664rresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views43479Altmetric-Citations3379LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Aromatic compounds,Catalysts,Cross coupling reaction,Reaction products Get e-Alerts

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Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members of the ECM family. Proteins/glycoproteins, such as collagens, elastin, laminins and tenascins, proteoglycans and glycosaminoglycans, hyaluronan, and their cell receptors such as CD44 and integrins, responsible for cell adhesion, comprise a well-organized functional network with significant roles in health and disease. On the other hand, enzymes such as matrix metalloproteinases and specific glycosidases including heparanase and hyaluronidases contribute to matrix remodeling and affect human health. Several cell processes and functions, among them cell proliferation and survival, migration, differentiation, autophagy, angiogenesis, and immunity regulation are affected by certain matrix components. Structural alterations have been also well associated with disease progression. This guide on the composition and functions of the ECM gives a broad overview of the matrisome, the major ECM macromolecules, and their interaction networks within the ECM and with the cell surface, summarizes their main structural features and their roles in tissue organization and cell functions, and emphasizes the importance of specific ECM constituents in disease development and progression as well as the advances in molecular targeting of ECM to design new therapeutic strategies.

Transition-metal-catalyzed C-H activation has recently emerged as a powerful tool for the functionalization of organic molecules. While many efforts have focused on the functionalization of arenes and heteroarenes by this strategy in the past two decades, much less research has been devoted to the activation of non-acidic C-H bonds of alkyl groups. This Minireview highlights recent work in this area, with a particular emphasis on synthetically useful methods.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous CatalysisFabienne Fache, Emmanuelle Schulz, M. Lorraine Tommasino, and Marc LemaireView Author Information Laboratoire de Catalyse et Synthèse Organique, UMR 5622, UCBL, CPE, 43 Bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France Cite this: Chem. Rev. 2000, 100, 6, 2159–2232Publication Date (Web):May 16, 2000Publication History Received2 December 1999Published online16 May 2000Published inissue 1 June 2000https://pubs.acs.org/doi/10.1021/cr9902897https://doi.org/10.1021/cr9902897research-articleACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views9177Altmetric-Citations809LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Catalysts,Chemical structure,Ligands,Selectivity,Stereoselectivity Get e-Alerts

Transition-metal-catalyzed C-H bond arylation has recently emerged as a powerful tool for the functionalization of organic molecules that may complement or even replace traditional catalytic cross-couplings. While many efforts have focused on the arylation of arenes and heteroarenes in the past two decades, less studies have been devoted to the arylation of nonacidic C-H bonds of alkyl groups. This tutorial review highlights recent work in this active area.

Multivalency plays a major role in biological processes and particularly in the relationship between pathogenic microorganisms and their host that involves protein-glycan recognition. These interactions occur during the first steps of infection, for specific recognition between host and bacteria, but also at different stages of the immune response. The search for high-affinity ligands for studying such interactions involves the combination of carbohydrate head groups with different scaffolds and linkers generating multivalent glycocompounds with controlled spatial and topology parameters. By interfering with pathogen adhesion, such glycocompounds including glycopolymers, glycoclusters, glycodendrimers and glyconanoparticles have the potential to improve or replace antibiotic treatments that are now subverted by resistance. Multivalent glycoconjugates have also been used for stimulating the innate and adaptive immune systems, for example with carbohydrate-based vaccines. Bacteria present on their surfaces natural multivalent glycoconjugates such as lipopolysaccharides and S-layers that can also be exploited or targeted in anti-infectious strategies.

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Abstract This review highlights some remarkable recently made achievements in the application of palladium‐mediated processes to the design of multicomponent one‐pot syntheses of heterocyclic compounds. Palladium‐catalysed cascade reactions are surveyed, together with processes based on sequential, one‐pot performance of individual transformations in which at least one is catalysed by palladium. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as the CF(3) source and MeOH as the reductant is disclosed. This effective transformation operates at room temperature in the presence of 5 mol % Ru(bpy)(3)Cl(2); the process is characterized by its operational simplicity and functional group tolerance.

The IntAct molecular interaction database (https://www.ebi.ac.uk/intact) is a curated resource of molecular interactions, derived from the scientific literature and from direct data depositions. As of August 2021, IntAct provides more than one million binary interactions, curated by twelve global partners of the International Molecular Exchange consortium, for which the IntAct database provides a shared curation and dissemination platform. The IMEx curation policy has always emphasised a fine-grained data and curation model, aiming to capture the relevant experimental detail essential for the interpretation of the provided molecular interaction data. Here, we present recent curation focus and progress, as well as a completely redeveloped website which presents IntAct data in a much more user-friendly and detailed way.

Abstract Because of its high lipophilicity, the CF 3 S group has always interested chemists. However, strategies to introduce it into organic molecules have been, for the most part, reserved to specialized “fluorine chemists”. Recent published work has demystified these preconceived ideas by proposing new efficient methods or easy‐to‐handle reagents to enrich the toolbox of chemists. However, all these new concepts arise from the pioneering works of the past! In this review, we will do a “back to the future” by remembering the most significant results of the past and by presenting extensions and novelties of the present and for the future.

The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional structural network comprised of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins and proteinases. In recent years, the field of PGs has expanded rapidly. Due to their high structural complexity and heterogeneity, PGs mediate several homeostatic and pathological processes. PGs consist of a protein core and one or more covalently attached GAG chains, which provide the protein cores with the ability to interact with several proteins. The GAG building blocks of PGs significantly influence the chemical and functional properties of PGs. The primary goal of this comprehensive review is to summarize major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis, focusing on structural variability, structure-function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis. Recent insights related to exosome biogenesis, degradation, and cell signaling, their status as diagnostic tools and potential pharmacological targets in diseases as well as current applications in nanotechnology and biotechnology are addressed. Moreover, issues related to docking studies, molecular modeling, GAG/PG interaction networks, and their integration are discussed.

Organ in vitro synthesis is one of the last bottlenecks between tissue engineering and transplantation of synthetic organs. Bioprinting has proven its capacity to produce 3D objects composed of living cells but highly organized tissues such as full thickness skin (dermis + epidermis) are rarely attained. The focus of the present study is to demonstrate the capability of a newly developed ink formulation and the use of an open source printer, for the production of a really complete skin model. Proofs are given through immunostaining and electronic microscopy that the bioprinted skin presents all characteristics of human skin, both at the molecular and macromolecular level. Finally, the printability of large skin objects is demonstrated with the printing of an adult-size ear.

The lysyl oxidase family comprises five members in mammals, lysyl oxidase (LOX) and four lysyl oxidase like proteins (LOXL1-4). They are copper amine oxidases with a highly conserved catalytic domain, a lysine tyrosylquinone cofactor, and a conserved copper-binding site. They catalyze the first step of the covalent cross-linking of the extracellular matrix (ECM) proteins collagens and elastin, which contribute to ECM stiffness and mechanical properties. The role of LOX and LOXL2 in fibrosis, tumorigenesis, and metastasis, including changes in their expression level and their regulation of cell signaling pathways, have been extensively reviewed, and both enzymes have been identified as therapeutic targets. We review here the molecular features and three-dimensional structure/models of LOX and LOXLs, their role in ECM cross-linking, and the regulation of their cross-linking activity by ECM proteins, proteoglycans, and by inhibitors. We also make an overview of the major ECM cross-links, because they are the ultimate molecular readouts of LOX/LOXL activity in tissues. The recent 3D model of LOX, which recapitulates its known structural and biochemical features, will be useful to decipher the molecular mechanisms of LOX interaction with its various substrates, and to design substrate-specific inhibitors, which are potential antifibrotic and antitumor drugs.

An efficient catalytic system has been developed for the synthesis of benzocyclobutenes by C-H activation of methyl groups. The optimal conditions employed a combination of Pd(OAc) 2 and P ( t )Bu 3 as catalyst, K 2CO 3 as the base, and DMF as solvent. A variety of substituted BCB were obtained under these conditions with yields in the 44-92% range, including molecules that are hardly accessible by other methods. The reaction was found limited to substrates bearing a quaternary benzylic carbon, but benzocyclobutenes bearing a tertiary benzylic carbon could be obtained indirectly from diesters by decarboxylation. Reaction substrates bearing a small substituent para to bromine gave an unexpected regioisomer that likely arose from a 1,4-palladium migration process. The formation of this "abnormal" regioisomer could be suppressed by introducing a larger subsituent para to bromine. DFT(B3PW91) calculations on the reaction of 2-bromo-tert-butylbenzene with Pd(P ( t )Bu 3) with different bases (acetate, bicarbonate, carbonate) showed the critical influence of the coordination mode of the base to induce both an easy C-H activation and to allow for a pathway for 1,4-palladium migration. Carbonate is shown to be more efficient than the two other bases because it can abstract the proton easily and at the same time maintain kappa (1)-coordination without extensive electronic reorganization.

Versatile strategies of multicomponent coupling reactions to synthesize variously substituted pyrroles 1 are summarized. These heterocycles are important targets as molecules in their own right, for their pharmacological properties, as well as intermediates for more elaborate syntheses.

Closer to nature: Biaryl motifs are common in organic molecules with important biological and physical properties. Carboxylic acids can now be used as aryl donors in palladium-catalyzed cross-coupling reactions to give biaryl compounds of high synthetic value (see scheme).

This Review summarizes close to 500 primary publications and surveys published since 2000 about the syntheses and diverse bioactivities of C-glycopyranosyl (het)arenes. A classification of the preparative routes to these synthetic targets according to methodologies and compound categories is provided. Several of these compounds, regardless of their natural or synthetic origin, display antidiabetic properties due to enzyme inhibition (glycogen phosphorylase, protein tyrosine phosphatase 1B) or by inhibiting renal sodium-dependent glucose cotransporter 2 (SGLT2). The latter class of synthetic inhibitors, very recently approved as antihyperglycemic drugs, opens new perspectives in the pharmacological treatment of type 2 diabetes. Various compounds with the C-glycopyranosyl (het)arene motif were subjected to biological studies displaying among others antioxidant, antiviral, antibiotic, antiadhesive, cytotoxic, and glycoenzyme inhibitory effects.

SEE SCHRAG AND POLITIS DOI101093/AWW190 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Apathy, which can occur separately or in combination with depression and anxiety, is one of the most frequently encountered neuropsychiatric symptoms in Parkinson's disease. Pathophysiological evidence suggests that parkinsonian apathy is primarily due to a mesolimbic dopaminergic denervation, but the role of the serotonergic alteration has never been examined, despite its well-known involvement in the pathogenesis of depression and anxiety. To fill this gap, we address here the pure model of de novo Parkinson's disease, without the confounding effects of antiparkinsonian treatment. Fifteen apathetic (Lille Apathy Rating Scale scores ≥ -21) and 15 non-apathetic (-36 ≤ Lille Apathy Rating Scale scores ≤ -22) drug-naïve de novo parkinsonian patients were enrolled in the present study and underwent detailed clinical assessment and positron emission tomography imaging, using both dopaminergic [(11)C-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane (PE2I)] (n = 29) and serotonergic [(11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine (DASB)] (n = 27) presynaptic transporter radioligands. Apathetic parkinsonian patients presented higher depression (P = 0.0004) and anxiety (P = 0.004) scores - as assessed using the Beck Depression Inventory and the part B of the State-Trait Anxiety Inventory, respectively - compared to the non-apathetic ones - who were not different from the age-matched healthy subjects (n = 15). Relative to the controls, the non-apathetic parkinsonian patients mainly showed dopaminergic denervation (n = 14) within the right caudate nucleus, bilateral putamen, thalamus and pallidum, while serotonergic innervation (n = 15) was fairly preserved. Apathetic parkinsonian patients exhibited, compared to controls, combined and widespread dopaminergic (n = 15) and serotonergic (n = 12) degeneration within the bilateral caudate nuclei, putamen, ventral striatum, pallidum and thalamus, but also a specific bilateral dopaminergic disruption within the substantia nigra-ventral tegmental area complex, as well as a specific serotonergic alteration within the insula, the orbitofrontal and the subgenual anterior cingulate cortices. When comparing the two parkinsonian groups, the apathetic patients mainly displayed greater serotonergic alteration in the ventral striatum, the dorsal and the subgenual parts of the anterior cingulate cortices, bilaterally, as well as in the right-sided caudate nucleus and the right-sided orbitofrontal cortex. Regression analyses also revealed that the severity of apathy was moreover mainly related to specific serotonergic lesions within the right-sided anterior caudate nucleus and the orbitofrontal cortex, while the degree of both depression and anxiety was primarily linked to serotonergic disruption within the bilateral subgenual parts and/or the right dorsal part of the anterior cingulate cortex, without prominent role of the dopaminergic degeneration in the pathogenesis of these three non-motor signs. Altogether, these findings highlight a prominent role of the serotonergic degeneration in the expression of the neuropsychiatric symptoms occurring at the onset of Parkinson's disease.