8 research outputs found
Conception et synthÚse de nouveaux Bambusurils pour des applications en biologie et en imagerie moléculaire
Design and synthesis of new Bambusurils for biological applications and molecular imagingBambus[n]urils, RâBU[4] and RââBU[6], are synthetic cyclic macromolecules that belong to the cucurbit[n]urils families. They are composed of n-substituted glycoluril units connected via n-methylene bridges. The RââBU[6], are able to bind anion inside their cavity with a good association constant through hydrogen bonds.In our laboratory, bambusurils bearing allyl functions, named AllylâBU[4] and AllylââBU[6], were efficiently prepared. These bambusurils were functionalized by ring-closing metathesis or thiol-ene click coupling to introduce 1 to 12 functions like ester, acids and glycosides.To develop the family of bambusurils, new bambusurils with propargyl functions were synthesized. The synthesis of the PropargylâBU[4] and PropargylââBU[6] were optimized. Theses BUs were functionalized by click chemistry with different azides like ester, benzyl and glycoside to dispose of new multivalent systems with a valency of 8 for the BU[4] and 12 for the BU[6]. For the first time, glycoBambusurils functionalized with D-mannose derivatives were prepared, and their antibacterial activities were assayed. Moreover, iminosugar from the family of the azido alkylated dĂ©oxynojirimycine, were grafted on the PropargylBUs to afford new inhibitors of glycosidases. These results show the importance of bambusuril scaffold and of the multivalence effect improve the affinity of the glycoBUs for the target.The association constants of RââBU[6] functionalized, soluble in aqueous media for iodide were determined by isothermal titration calorimetry. The results show a good affinity of R12BU[6] for iodide (Ka â 10â” Mâ»Âč).We studied as well an application of bambusuril for molecular imaging. A new bambusuril with biological ligands was designed and synthesized to introduce a bimodal probe PET/Optical in the last step. This probe will allow the combination of clinical diagnostic with PET and optical imaging. A proof of concept was realized with a function ÂčâžF labelled.Conception et synthĂšse de nouveaux Bambusurils pour des applications en biologie et en imagerie molĂ©culaire. Les bambusurils, RâBU[4] et RââBU[6], sont des molĂ©cules cages synthĂ©tiques, constituĂ©es respectivement de 4 et 6 unitĂ©s glycolurils. Ils diffĂšrent des cucurbiturils par la prĂ©sence de glycolurils difonctionnalisĂ©s qui leur confĂšrent une topologie de type alternĂ©e et des propriĂ©tĂ©s supramolĂ©culaires intĂ©ressantes. Les RââBU[6] ont la capacitĂ© dâencapsuler un anion Ă l'intĂ©rieur de leur cavitĂ© avec une trĂšs grande affinitĂ© grĂące Ă 12 liaisons hydrogĂšnes. Au laboratoire, des bambusurils disposant de groupements allyles nommĂ©s AllylâBU[4] et AllylââBU[6] ont Ă©tĂ© synthĂ©tisĂ©s. Ils ont ensuite Ă©tĂ© fonctionnalisĂ©s par rĂ©actions de mĂ©tathĂšse croisĂ©e et de thiol-Ăšne click pour introduire facilement 8 Ă 12 thiols d'intĂ©rĂȘts possĂ©dant des groupements esters, acides ou glycosides. Pour Ă©largir la famille des bambusurils, de nouveaux bambusurils possĂ©dant des fonctions propargyliques ont Ă©tĂ© prĂ©parĂ©s. Ainsi, les PropargylâBU[4] et PropargylââBU[6] ont Ă©tĂ© obtenus avec de bons rendements. Ces bambusurils ont ensuite Ă©tĂ© post-fonctionnalisĂ©s avec diffĂ©rents azotures (esters, benzyl, glycosides, peptides) par rĂ©action de chimie click pour conduire Ă de nouvelles plateformes multivalentes de valence 8 pour le BU[4] et 12 pour le BU[6]. Des glycoBUs fonctionnalisĂ©s par des dĂ©rivĂ©s du D-mannose ont Ă©tĂ© synthĂ©tisĂ©s pour la premiĂšre fois, et leur activitĂ© antibactĂ©rienne a Ă©tĂ© Ă©valuĂ©e. De plus, des iminosucres de la famille de la dĂ©oxynojirimycine azidoalkylĂ©e, ont Ă©galement Ă©tĂ© greffĂ©s sur les PropargylBUs, pour conduire Ă de nouveaux inhibiteurs de glycosidases. Le squelette des bambusurils et la multivalence conduisent Ă des gains d'affinitĂ© importants par rapport aux analogues glycosides monovalents.L'affinitĂ© des RââBU[6], hydrosolubles, a Ă©tĂ© Ă©valuĂ©e pour les ions iodures par titration calorimĂ©trique isotherme. Les rĂ©sultats obtenus confirment la grande affinitĂ© des BU[6] pour cet anion dans l'eau (Ka â 10â” Mâ»Âč).Une derniĂšre application des bambusurils comme sonde d'imagerie a Ă©galement Ă©tĂ© Ă©tudiĂ©e. Un nouveau bambusuril diffĂ©remment substituĂ© a Ă©tĂ© conçu et synthĂ©tisĂ© pour permettre l'introduction d'une sonde bimodale TEP/Optique en derniĂšre Ă©tape de synthĂšse. Cette sonde permettra la combinaison d'un double diagnostic mĂ©dical par imagerie TEP et optique. Une preuve de concept a Ă©tĂ© rĂ©alisĂ©e avec l'introduction d'un groupement radiomarquĂ© au ÂčâžF
Conception et synthÚse de nouveaux Bambusurils pour des applications en biologie et en imagerie moléculaire
Design and synthesis of new Bambusurils for biological applications and molecular imagingBambus[n]urils, RâBU[4] and RââBU[6], are synthetic cyclic macromolecules that belong to the cucurbit[n]urils families. They are composed of n-substituted glycoluril units connected via n-methylene bridges. The RââBU[6], are able to bind anion inside their cavity with a good association constant through hydrogen bonds.In our laboratory, bambusurils bearing allyl functions, named AllylâBU[4] and AllylââBU[6], were efficiently prepared. These bambusurils were functionalized by ring-closing metathesis or thiol-ene click coupling to introduce 1 to 12 functions like ester, acids and glycosides.To develop the family of bambusurils, new bambusurils with propargyl functions were synthesized. The synthesis of the PropargylâBU[4] and PropargylââBU[6] were optimized. Theses BUs were functionalized by click chemistry with different azides like ester, benzyl and glycoside to dispose of new multivalent systems with a valency of 8 for the BU[4] and 12 for the BU[6]. For the first time, glycoBambusurils functionalized with D-mannose derivatives were prepared, and their antibacterial activities were assayed. Moreover, iminosugar from the family of the azido alkylated dĂ©oxynojirimycine, were grafted on the PropargylBUs to afford new inhibitors of glycosidases. These results show the importance of bambusuril scaffold and of the multivalence effect improve the affinity of the glycoBUs for the target.The association constants of RââBU[6] functionalized, soluble in aqueous media for iodide were determined by isothermal titration calorimetry. The results show a good affinity of R12BU[6] for iodide (Ka â 10â” Mâ»Âč).We studied as well an application of bambusuril for molecular imaging. A new bambusuril with biological ligands was designed and synthesized to introduce a bimodal probe PET/Optical in the last step. This probe will allow the combination of clinical diagnostic with PET and optical imaging. A proof of concept was realized with a function ÂčâžF labelled.Conception et synthĂšse de nouveaux Bambusurils pour des applications en biologie et en imagerie molĂ©culaire. Les bambusurils, RâBU[4] et RââBU[6], sont des molĂ©cules cages synthĂ©tiques, constituĂ©es respectivement de 4 et 6 unitĂ©s glycolurils. Ils diffĂšrent des cucurbiturils par la prĂ©sence de glycolurils difonctionnalisĂ©s qui leur confĂšrent une topologie de type alternĂ©e et des propriĂ©tĂ©s supramolĂ©culaires intĂ©ressantes. Les RââBU[6] ont la capacitĂ© dâencapsuler un anion Ă l'intĂ©rieur de leur cavitĂ© avec une trĂšs grande affinitĂ© grĂące Ă 12 liaisons hydrogĂšnes. Au laboratoire, des bambusurils disposant de groupements allyles nommĂ©s AllylâBU[4] et AllylââBU[6] ont Ă©tĂ© synthĂ©tisĂ©s. Ils ont ensuite Ă©tĂ© fonctionnalisĂ©s par rĂ©actions de mĂ©tathĂšse croisĂ©e et de thiol-Ăšne click pour introduire facilement 8 Ă 12 thiols d'intĂ©rĂȘts possĂ©dant des groupements esters, acides ou glycosides. Pour Ă©largir la famille des bambusurils, de nouveaux bambusurils possĂ©dant des fonctions propargyliques ont Ă©tĂ© prĂ©parĂ©s. Ainsi, les PropargylâBU[4] et PropargylââBU[6] ont Ă©tĂ© obtenus avec de bons rendements. Ces bambusurils ont ensuite Ă©tĂ© post-fonctionnalisĂ©s avec diffĂ©rents azotures (esters, benzyl, glycosides, peptides) par rĂ©action de chimie click pour conduire Ă de nouvelles plateformes multivalentes de valence 8 pour le BU[4] et 12 pour le BU[6]. Des glycoBUs fonctionnalisĂ©s par des dĂ©rivĂ©s du D-mannose ont Ă©tĂ© synthĂ©tisĂ©s pour la premiĂšre fois, et leur activitĂ© antibactĂ©rienne a Ă©tĂ© Ă©valuĂ©e. De plus, des iminosucres de la famille de la dĂ©oxynojirimycine azidoalkylĂ©e, ont Ă©galement Ă©tĂ© greffĂ©s sur les PropargylBUs, pour conduire Ă de nouveaux inhibiteurs de glycosidases. Le squelette des bambusurils et la multivalence conduisent Ă des gains d'affinitĂ© importants par rapport aux analogues glycosides monovalents.L'affinitĂ© des RââBU[6], hydrosolubles, a Ă©tĂ© Ă©valuĂ©e pour les ions iodures par titration calorimĂ©trique isotherme. Les rĂ©sultats obtenus confirment la grande affinitĂ© des BU[6] pour cet anion dans l'eau (Ka â 10â” Mâ»Âč).Une derniĂšre application des bambusurils comme sonde d'imagerie a Ă©galement Ă©tĂ© Ă©tudiĂ©e. Un nouveau bambusuril diffĂ©remment substituĂ© a Ă©tĂ© conçu et synthĂ©tisĂ© pour permettre l'introduction d'une sonde bimodale TEP/Optique en derniĂšre Ă©tape de synthĂšse. Cette sonde permettra la combinaison d'un double diagnostic mĂ©dical par imagerie TEP et optique. Une preuve de concept a Ă©tĂ© rĂ©alisĂ©e avec l'introduction d'un groupement radiomarquĂ© au ÂčâžF
Conception et synthÚse de nouveaux Bambusurils pour des applications en biologie et en imagerie moléculaire
Design and synthesis of new Bambusurils for biological applications and molecular imagingBambus[n]urils, RâBU[4] and RââBU[6], are synthetic cyclic macromolecules that belong to the cucurbit[n]urils families. They are composed of n-substituted glycoluril units connected via n-methylene bridges. The RââBU[6], are able to bind anion inside their cavity with a good association constant through hydrogen bonds.In our laboratory, bambusurils bearing allyl functions, named AllylâBU[4] and AllylââBU[6], were efficiently prepared. These bambusurils were functionalized by ring-closing metathesis or thiol-ene click coupling to introduce 1 to 12 functions like ester, acids and glycosides.To develop the family of bambusurils, new bambusurils with propargyl functions were synthesized. The synthesis of the PropargylâBU[4] and PropargylââBU[6] were optimized. Theses BUs were functionalized by click chemistry with different azides like ester, benzyl and glycoside to dispose of new multivalent systems with a valency of 8 for the BU[4] and 12 for the BU[6]. For the first time, glycoBambusurils functionalized with D-mannose derivatives were prepared, and their antibacterial activities were assayed. Moreover, iminosugar from the family of the azido alkylated dĂ©oxynojirimycine, were grafted on the PropargylBUs to afford new inhibitors of glycosidases. These results show the importance of bambusuril scaffold and of the multivalence effect improve the affinity of the glycoBUs for the target.The association constants of RââBU[6] functionalized, soluble in aqueous media for iodide were determined by isothermal titration calorimetry. The results show a good affinity of R12BU[6] for iodide (Ka â 10â” Mâ»Âč).We studied as well an application of bambusuril for molecular imaging. A new bambusuril with biological ligands was designed and synthesized to introduce a bimodal probe PET/Optical in the last step. This probe will allow the combination of clinical diagnostic with PET and optical imaging. A proof of concept was realized with a function ÂčâžF labelled.Conception et synthĂšse de nouveaux Bambusurils pour des applications en biologie et en imagerie molĂ©culaire. Les bambusurils, RâBU[4] et RââBU[6], sont des molĂ©cules cages synthĂ©tiques, constituĂ©es respectivement de 4 et 6 unitĂ©s glycolurils. Ils diffĂšrent des cucurbiturils par la prĂ©sence de glycolurils difonctionnalisĂ©s qui leur confĂšrent une topologie de type alternĂ©e et des propriĂ©tĂ©s supramolĂ©culaires intĂ©ressantes. Les RââBU[6] ont la capacitĂ© dâencapsuler un anion Ă l'intĂ©rieur de leur cavitĂ© avec une trĂšs grande affinitĂ© grĂące Ă 12 liaisons hydrogĂšnes. Au laboratoire, des bambusurils disposant de groupements allyles nommĂ©s AllylâBU[4] et AllylââBU[6] ont Ă©tĂ© synthĂ©tisĂ©s. Ils ont ensuite Ă©tĂ© fonctionnalisĂ©s par rĂ©actions de mĂ©tathĂšse croisĂ©e et de thiol-Ăšne click pour introduire facilement 8 Ă 12 thiols d'intĂ©rĂȘts possĂ©dant des groupements esters, acides ou glycosides. Pour Ă©largir la famille des bambusurils, de nouveaux bambusurils possĂ©dant des fonctions propargyliques ont Ă©tĂ© prĂ©parĂ©s. Ainsi, les PropargylâBU[4] et PropargylââBU[6] ont Ă©tĂ© obtenus avec de bons rendements. Ces bambusurils ont ensuite Ă©tĂ© post-fonctionnalisĂ©s avec diffĂ©rents azotures (esters, benzyl, glycosides, peptides) par rĂ©action de chimie click pour conduire Ă de nouvelles plateformes multivalentes de valence 8 pour le BU[4] et 12 pour le BU[6]. Des glycoBUs fonctionnalisĂ©s par des dĂ©rivĂ©s du D-mannose ont Ă©tĂ© synthĂ©tisĂ©s pour la premiĂšre fois, et leur activitĂ© antibactĂ©rienne a Ă©tĂ© Ă©valuĂ©e. De plus, des iminosucres de la famille de la dĂ©oxynojirimycine azidoalkylĂ©e, ont Ă©galement Ă©tĂ© greffĂ©s sur les PropargylBUs, pour conduire Ă de nouveaux inhibiteurs de glycosidases. Le squelette des bambusurils et la multivalence conduisent Ă des gains d'affinitĂ© importants par rapport aux analogues glycosides monovalents.L'affinitĂ© des RââBU[6], hydrosolubles, a Ă©tĂ© Ă©valuĂ©e pour les ions iodures par titration calorimĂ©trique isotherme. Les rĂ©sultats obtenus confirment la grande affinitĂ© des BU[6] pour cet anion dans l'eau (Ka â 10â” Mâ»Âč).Une derniĂšre application des bambusurils comme sonde d'imagerie a Ă©galement Ă©tĂ© Ă©tudiĂ©e. Un nouveau bambusuril diffĂ©remment substituĂ© a Ă©tĂ© conçu et synthĂ©tisĂ© pour permettre l'introduction d'une sonde bimodale TEP/Optique en derniĂšre Ă©tape de synthĂšse. Cette sonde permettra la combinaison d'un double diagnostic mĂ©dical par imagerie TEP et optique. Une preuve de concept a Ă©tĂ© rĂ©alisĂ©e avec l'introduction d'un groupement radiomarquĂ© au ÂčâžF
Design and synthesis of new Bambusurils for biological applications and molecular imaging
Conception et synthĂšse de nouveaux Bambusurils pour des applications en biologie et en imagerie molĂ©culaire. Les bambusurils, RâBU[4] et RââBU[6], sont des molĂ©cules cages synthĂ©tiques, constituĂ©es respectivement de 4 et 6 unitĂ©s glycolurils. Ils diffĂšrent des cucurbiturils par la prĂ©sence de glycolurils difonctionnalisĂ©s qui leur confĂšrent une topologie de type alternĂ©e et des propriĂ©tĂ©s supramolĂ©culaires intĂ©ressantes. Les RââBU[6] ont la capacitĂ© dâencapsuler un anion Ă l'intĂ©rieur de leur cavitĂ© avec une trĂšs grande affinitĂ© grĂące Ă 12 liaisons hydrogĂšnes. Au laboratoire, des bambusurils disposant de groupements allyles nommĂ©s AllylâBU[4] et AllylââBU[6] ont Ă©tĂ© synthĂ©tisĂ©s. Ils ont ensuite Ă©tĂ© fonctionnalisĂ©s par rĂ©actions de mĂ©tathĂšse croisĂ©e et de thiol-Ăšne click pour introduire facilement 8 Ă 12 thiols d'intĂ©rĂȘts possĂ©dant des groupements esters, acides ou glycosides. Pour Ă©largir la famille des bambusurils, de nouveaux bambusurils possĂ©dant des fonctions propargyliques ont Ă©tĂ© prĂ©parĂ©s. Ainsi, les PropargylâBU[4] et PropargylââBU[6] ont Ă©tĂ© obtenus avec de bons rendements. Ces bambusurils ont ensuite Ă©tĂ© post-fonctionnalisĂ©s avec diffĂ©rents azotures (esters, benzyl, glycosides, peptides) par rĂ©action de chimie click pour conduire Ă de nouvelles plateformes multivalentes de valence 8 pour le BU[4] et 12 pour le BU[6]. Des glycoBUs fonctionnalisĂ©s par des dĂ©rivĂ©s du D-mannose ont Ă©tĂ© synthĂ©tisĂ©s pour la premiĂšre fois, et leur activitĂ© antibactĂ©rienne a Ă©tĂ© Ă©valuĂ©e. De plus, des iminosucres de la famille de la dĂ©oxynojirimycine azidoalkylĂ©e, ont Ă©galement Ă©tĂ© greffĂ©s sur les PropargylBUs, pour conduire Ă de nouveaux inhibiteurs de glycosidases. Le squelette des bambusurils et la multivalence conduisent Ă des gains d'affinitĂ© importants par rapport aux analogues glycosides monovalents.L'affinitĂ© des RââBU[6], hydrosolubles, a Ă©tĂ© Ă©valuĂ©e pour les ions iodures par titration calorimĂ©trique isotherme. Les rĂ©sultats obtenus confirment la grande affinitĂ© des BU[6] pour cet anion dans l'eau (Ka â 10â” Mâ»Âč).Une derniĂšre application des bambusurils comme sonde d'imagerie a Ă©galement Ă©tĂ© Ă©tudiĂ©e. Un nouveau bambusuril diffĂ©remment substituĂ© a Ă©tĂ© conçu et synthĂ©tisĂ© pour permettre l'introduction d'une sonde bimodale TEP/Optique en derniĂšre Ă©tape de synthĂšse. Cette sonde permettra la combinaison d'un double diagnostic mĂ©dical par imagerie TEP et optique. Une preuve de concept a Ă©tĂ© rĂ©alisĂ©e avec l'introduction d'un groupement radiomarquĂ© au ÂčâžF.Design and synthesis of new Bambusurils for biological applications and molecular imagingBambus[n]urils, RâBU[4] and RââBU[6], are synthetic cyclic macromolecules that belong to the cucurbit[n]urils families. They are composed of n-substituted glycoluril units connected via n-methylene bridges. The RââBU[6], are able to bind anion inside their cavity with a good association constant through hydrogen bonds.In our laboratory, bambusurils bearing allyl functions, named AllylâBU[4] and AllylââBU[6], were efficiently prepared. These bambusurils were functionalized by ring-closing metathesis or thiol-ene click coupling to introduce 1 to 12 functions like ester, acids and glycosides.To develop the family of bambusurils, new bambusurils with propargyl functions were synthesized. The synthesis of the PropargylâBU[4] and PropargylââBU[6] were optimized. Theses BUs were functionalized by click chemistry with different azides like ester, benzyl and glycoside to dispose of new multivalent systems with a valency of 8 for the BU[4] and 12 for the BU[6]. For the first time, glycoBambusurils functionalized with D-mannose derivatives were prepared, and their antibacterial activities were assayed. Moreover, iminosugar from the family of the azido alkylated dĂ©oxynojirimycine, were grafted on the PropargylBUs to afford new inhibitors of glycosidases. These results show the importance of bambusuril scaffold and of the multivalence effect improve the affinity of the glycoBUs for the target.The association constants of RââBU[6] functionalized, soluble in aqueous media for iodide were determined by isothermal titration calorimetry. The results show a good affinity of R12BU[6] for iodide (Ka â 10â” Mâ»Âč).We studied as well an application of bambusuril for molecular imaging. A new bambusuril with biological ligands was designed and synthesized to introduce a bimodal probe PET/Optical in the last step. This probe will allow the combination of clinical diagnostic with PET and optical imaging. A proof of concept was realized with a function ÂčâžF labelled
Bambus[4,6]urils as Dual Scaffolds for Multivalent Iminosugar Presentation and Ion Transport: Access to Unprecedented Glycosidase-Directed Anion Caging Agents
Bambusurils, BU[4] and BU[6], were used for the first time as multivalent scaffolds to link glycosidases inhibitors derived from 1-deoxynojirimycin (DNJ). Two linear DNJ ligands having six or nine carbon alkyl azido linkers or a trivalent DNJ dendron were grafted onto octapropargylated BU[4] and dodecapropargylated BU[6] using copper-catalyzed cycloaddition (CuAAC) to yield corresponding neoglycobambus[4] and neoglycobambus[6]urils bearing 8 to 24 iminosugars. The inhibition potencies of neoglycoBU[4], neoglycoBU[6] and neoglycoBU[6] caging anions were evaluated against Jack Bean α-mannosidase and compared to monovalent DNJ derivatives. Strong affinity enhancements per inhibitory head were obtained for the clusters holding trivalent dendrons with inhibitory constants in the nanomolar range (Ki = 24 nM for BU[4] with 24 DNJ units). Interestingly, the anion (bromide or iodide) encapsulated inside the cavity of BU[6] does not modify the inhibition potency of neoglycoBU[6], opening the way to water-soluble glycosidase-directed anion caging agents that may find applications in important fields such as bio(in)organic chemistry or oncology
Functionalization of Bambusurils by a thiol-ene click reaction and a facile method for the preparation of anion-free Bambus[6]urils
International audienceNew sulfideâfunctionalized bambus[4]urils ((RS)BU[4]) and bambus[6]urils ((RS)BU[6]) have been synthesized through thiolâene click coupling reactions (TEC) of allylbambus[n]urils. Synthesis of BU[6] derivatives always requires the use of a template anion (iodide, chloride or bromide) which is enclosed in the cavity of BU[6]. We show that this anion influences the reactivity of bambus[6]urils. An encapsulated iodide makes allyl functions of allylBU[6] less reactive towards TEC and hydrogenation reactions in comparison to the corresponding chloride or bromide inclusion complexes. This is critical for the chemical reactivity of BU[6] and even more to determine their anionâbinding properties. We report a new, facile and fast method using AgSbF to prepare anionâfree BU[6]. NMR methods were used to estimate association constants of these new empty BU[6] with different anions. Quantum chemistry calculations were employed to rationalize the observed results. These new functionalized bambusuril scaffolds in alternate conformation could find applications as multivalent binders
Clickable Bambusurils to Access Multivalent Architectures
Publisher: American Chemical SocietyInternational audiencePropargylated bambus[4,6]urils were prepared by an efficient one-step condensation of dipropargylglycoluril with formaldehyde under microwave irradiation. Their functionalization by click chemistry (CuAAC) afforded new multivalent architectures decorated with 8 or 12 ligands. Grafting of glycosides provided water-soluble glycobambus[4,6]uril platforms with glucosyl12BU[6] showing good affinity toward iodide anion in aqueous medium