Yves Dory - Academia.edu (original) (raw)
Papers by Yves Dory
![Research paper thumbnail of Systematic replacement of amides by 1,4-disubstituted[1,2,3]triazoles in Leu-enkephalin and the impact on the delta opioid receptor activity](https://attachments.academia-assets.com/119686803/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry Letters, 2013
Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid pha... more Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.
ACS Chemical Neuroscience, 2019
Leu-enkephalin and D-Ala 2-Leu-Enkephalin were modified at their N-and C-termini with guanidyl an... more Leu-enkephalin and D-Ala 2-Leu-Enkephalin were modified at their N-and C-termini with guanidyl and tetrazole groups. The resulting molecules were prepared in solution or by solid phase peptide synthesis. The affinity of the different analogs at mu (MOP) and delta opioid receptors (DOP) was then
Chemistry – A European Journal, 2019
Cyclohexane and cyclotri-b-alanyl have been used as scaffolds for the design of novel C3-symetric... more Cyclohexane and cyclotri-b-alanyl have been used as scaffolds for the design of novel C3-symetric rings incorporating conjugated alkenes and dienes. All three C3-symmetric lactams share the same triangular shape and their crystal system is trigonal. They all belong to the R3 space group, R3m, R3 and R3c respectively for the increasingly large 12-, 18-and 24-membered rigid rings. All lactams stack on top of each other, through H-bonds and van der Waals non-covalent interactions, leading to endless supramolecular cylinders and tubes. The largest member of the family leads to tubes, whose central pore is wide enough to let water in. A common feature of all the lactams is their very large dipole, of around 9 D according to DFT calculations. Surprisingly, all the resulting cylinders and tubes pack side by side in the crystals, with all the dipoles pointing to the same direction. As a result, all three crystals are anisotropic and appear to be the first members of a new kind of highly polar crystals.
Physical Review E, 2017
Diffusion in nature is usually considered as a smooth redistribution process. However, it appears... more Diffusion in nature is usually considered as a smooth redistribution process. However, it appears that the diffusion of chiral molecules and the propagation of chirality may proceed in quite different ways. Indeed, in the present work, unexpected quantization of the spatial concentration of chiral molecules is discovered in self-aligned molecular liquids. It is shown that the interpenetration of two liquids is forming discrete diffusion barrier walls resulting in steplike concentration distribution of chiral molecules in space. The concentration gradient is at least an order of magnitude stronger from both sides of the barrier wall compared to the gradient between those walls. It is also shown that this microscopic diffusion process may be controlled by macroscopic boundary conditions imposed on the host molecular system. Both of those phenomena are related to the collective long-range orientational "elastic" interactions of molecules of the host. The observed phenomena may radically change our understanding of diffusion of chiral molecules, among others, in biological tissue, which contains many examples of self-aligned molecular liquids. This, in turn, has the potential to revolutionize drug design and delivery techniques.
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Tetrahedron Letters, 2000
A sequence of ®ve chemical steps on solid support yields hydroxy-acids in a very straightforward ... more A sequence of ®ve chemical steps on solid support yields hydroxy-acids in a very straightforward and ecient manner. The resulting compounds can be cyclized in solution phase by forming an ester bond to produce macrolactones.
Tetrahedron, 1998
A sterically unbiased macrocyclic probe has been used to study the Diels-Alder reaction mechanism... more A sterically unbiased macrocyclic probe has been used to study the Diels-Alder reaction mechanism of enal dienophiles. All the results, theoretical as well as kinetical, converge to the conclusion that a virtually non-concerted zwitterionic mechanism is possible for certain ...
Tetrahedron, 2000
The relative rate of hydrolysis of these compounds is rationalized by considering the influence o... more The relative rate of hydrolysis of these compounds is rationalized by considering the influence of steric, inductive and stereoelectronic effects on the hydrolysis reaction mechanism.
Organic Letters, 2000
When phenyl triO -benzyl-1-thio-D-galactopyranosiduronic acid esters were coupled with a 1/1 mixt... more When phenyl triO -benzyl-1-thio-D-galactopyranosiduronic acid esters were coupled with a 1/1 mixture of r and 2,3 di-O-protected D-galactopyranosiduronic acid esters, the-anomer proved to be more reactive. Data from theoretical calculations suggested that the enhanced reactivity of this anomer compared with the r one would be due to a stronger hydrogen bond of the C-4 OH with the ring oxygen.
Journal of the American Chemical Society, 1995
ABSTRACT
Crystal Growth & Design, 2009
ABSTRACT Both macrolactams cyclo-[NH−CH2−C≡C−CH2−C(Me)2-CO]n (n = 3 and n = 2) have been synthesi... more ABSTRACT Both macrolactams cyclo-[NH−CH2−C≡C−CH2−C(Me)2-CO]n (n = 3 and n = 2) have been synthesized and crystallized. They have respectively one intramolecular hydrogen bond and no such bond. Both macrocycles self-assemble as parallel supramolecular walls with or without inclusion of solvent between them. The units of the former (n = 3) are held together by NH···π/NH···OC interactions, whereas they are glued by a very dense network of classical parallel-oriented hydrogen bonds, involving all the amides of the rings, in the latter (n = 2). In that case, the bulky C(Me)2 groups are located on the surface of the walls and can be held responsible for the piling process of the layers, by means of attractive van der Waals interactions. This spatial arrangement recalls the 3D structure of cellulose, where all constitutive sheets stack mostly via van der Waals forces.
Chemistry - A European Journal, 2007
The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n... more The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n=2; 2, n=3; 3, n=4) and cyclo-[NH-CH(2)-CH(2)-CH=CH-CO](3) (4) has been achieved by two approaches. A linear route leads to precursors that are subsequently macrocyclized in a separate step. The second, convergent approach relies on the symmetry of the targets: it includes suitably activated subunits, which are subjected to macrocyclization conditions. The subunits first oligomerize, then cyclize to form either pure macrolactams or mixtures. The macrolactam units 1, 2 and 4 stack on top each other through weak interactions (hydrogen bond and van der Waals), to form endless square, rectangular and triangular prisms, respectively. These stacks are further packed side by side in crystals grown from isotropic media. The overall dipoles in the crystals from lactams 1 and 4, which result mostly from the alignment of amide groups, are zero and large, respectively. Macrolactam 2 displays an astonishing isomorphism when allowed to cool down in anisotropic liquid crystal solutions. Large hollow hexagonal tubes are then obtained through a fractal process. Contrary to the three previous rings, 3 yields crystals where prisms of any shape are absent.
Canadian Journal of Chemistry, 2002
Transannular DielsAlder (TADA) adducts constitute a collection of rigid structures, whose confor... more Transannular DielsAlder (TADA) adducts constitute a collection of rigid structures, whose conformational diversity is rich. It is possible to design such specifically functionalized molecules capable of binding to known biological targets by molecular modelling MCSSHOOK (multiple copy simultaneous search). Here we show that such carefully designed compounds can be easily built from small synthons. TADA adducts are very interesting due to their huge conformational diversity, their rigidity (biological interest), and their ease of synthesis (chemical interest).Key words: tricycles, synthesis, transannular DielsAlder, macrocyclization, conformation, diversity.
Acta Crystallographica Section E Crystallographic Communications, 2017
The crystal structures of tert-butyl (5-chloropenta-2,4-diyn-1-yl)carbamate, C10H12ClNO2 (II), an... more The crystal structures of tert-butyl (5-chloropenta-2,4-diyn-1-yl)carbamate, C10H12ClNO2 (II), and tert-butyl (5-iodopenta-2,4-diyn-1-yl)carbamate, C10H12INO2 (IV), are isomorphous to previously reported structures and accordingly their molecular and supramolecular structures are similar. In the crystals of (II) and (IV), molecules are linked into very similar two-dimensional wall organizations with antiparallel carbamate groups involved in a combination of hydrogen and halogen bonds (bifurcated N—H...O=C and C[triple-bond]C—X...O=C interactions on the same carbonyl group). There is no long-range parallel stacking of diynes, so the topochemical polymerization of diacetylene is prevented. A Cambridge Structural Database search revealed that C[triple-bond]C—X...O=C contacts shorter than the sum of the van der Waals radii are scarce (only one structure for the C[triple-bond]C—Cl...O=C interaction and 13 structures for the similar C[triple-bond]C—I...O=C interaction).
Organic Letters, 2017
Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (D... more Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (DOP), this compound was selected for the design of a novel 64 Cu-radiolabeled potent and selective DOP positron emission tomography (PET) imaging agent. Ex vivo autoradiography of TIPPD-PEG-K(NOTA/ 64 Cu)-NH 2 on rat brain sections produced a distribution pattern consistent with the known expression of DOP. Taken together, the in vitro and ex vivo data indicate that this 64 Cu-tracer holds promise for studying the DOP by means of PET.
Crystals, 2016
Isomorphous crystals of two diacetylene derivatives with carbamate functionality (BocNH-CH 2-diyn... more Isomorphous crystals of two diacetylene derivatives with carbamate functionality (BocNH-CH 2-diyne-X, where X = H or Br) have been obtained. The main feature of these structures is the original 2D arrangement (as supramolecular sheets or walls) in which the H bond and halogen bond have a prominent effect on the whole architecture. The two diacetylene compounds harbor neighboring carbamate (Boc protected amine) and conjugated alkyne functionalities. They differ only by the nature of the atom located at the penultimate position of the diyne moiety, either a hydrogen atom or a bromine atom. Both of them adopt very similar 2D wall organizations with antiparallel carbamates (as in antiparallel beta pleated sheets). Additional weak interactions inside the same walls between molecular bricks are H bond interactions (diyne-H¨¨¨O=C) or halogen bond interactions (diyne-Br¨¨¨O=C), respectively. Based on crystallographic atom coordinates, DFT (B3LYP/6-31++G(d,p)) and DFT (M06-2X/6-31++G(d,p)) calculations were performed on these isostructural crystals to gain insight into the intermolecular interactions.
Tetrahedron, 1998
Various 14-membered macrocyclic trienes underwent transannular Diels-Alder reactions to yield tet... more Various 14-membered macrocyclic trienes underwent transannular Diels-Alder reactions to yield tetracyclic structures that are stereoisomers of steroids. Due to the complexity of the effects at work during these reactions, a thorough molecular modeling study was carried out. Thus, some molecular mechanics, semiempirical and ab initio methods were compared and the results were finally used to rationalize the experimental results.
Peptides Across the Pacific: The Proceedings of the Twenty-Third American and the Sixth International Peptide Symposium, 2013
We extend to you a warm and sunny Aloha in celebration of the 23 rd American Peptide Symposium an... more We extend to you a warm and sunny Aloha in celebration of the 23 rd American Peptide Symposium and the 6 th International Symposium. The meeting theme, Peptides Across the Pacific, embraced the spirit of the scientific and social program. Peptides Across the Pacific encompassed the important role that peptide science currently plays in so many disciplines and explored the potential impact peptides can make in scientific fields that have yet to realize the utility of these wonderful molecules. The scientific program for 2013 was framed by distinguished lectures delivered by two renowned peptide chemists.
Bioorganic & Medicinal Chemistry Letters, 2013
Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid pha... more Using Cu(I)-catalyzed azide-alkyne cycloaddition in a mixed classical organic phase and solid phase peptide synthesis approach, we synthesized four analogs of Leu-enkephalin to systematically replace amides by 1,4-disubstituted[1,2,3]triazoles. The peptidomimetics obtained were characterized by competitive binding, contractility assays and ERK1/2 phosphorylation. The present study reveals that the analog bearing a triazole between Phe and Leu retains some potency, more than all the others, suggesting that the hydrogen bond acceptor capacity of the last amide of Leu-enkephalin is essential for the biological activity of the peptide.
ACS Chemical Neuroscience, 2019
Leu-enkephalin and D-Ala 2-Leu-Enkephalin were modified at their N-and C-termini with guanidyl an... more Leu-enkephalin and D-Ala 2-Leu-Enkephalin were modified at their N-and C-termini with guanidyl and tetrazole groups. The resulting molecules were prepared in solution or by solid phase peptide synthesis. The affinity of the different analogs at mu (MOP) and delta opioid receptors (DOP) was then
Chemistry – A European Journal, 2019
Cyclohexane and cyclotri-b-alanyl have been used as scaffolds for the design of novel C3-symetric... more Cyclohexane and cyclotri-b-alanyl have been used as scaffolds for the design of novel C3-symetric rings incorporating conjugated alkenes and dienes. All three C3-symmetric lactams share the same triangular shape and their crystal system is trigonal. They all belong to the R3 space group, R3m, R3 and R3c respectively for the increasingly large 12-, 18-and 24-membered rigid rings. All lactams stack on top of each other, through H-bonds and van der Waals non-covalent interactions, leading to endless supramolecular cylinders and tubes. The largest member of the family leads to tubes, whose central pore is wide enough to let water in. A common feature of all the lactams is their very large dipole, of around 9 D according to DFT calculations. Surprisingly, all the resulting cylinders and tubes pack side by side in the crystals, with all the dipoles pointing to the same direction. As a result, all three crystals are anisotropic and appear to be the first members of a new kind of highly polar crystals.
Physical Review E, 2017
Diffusion in nature is usually considered as a smooth redistribution process. However, it appears... more Diffusion in nature is usually considered as a smooth redistribution process. However, it appears that the diffusion of chiral molecules and the propagation of chirality may proceed in quite different ways. Indeed, in the present work, unexpected quantization of the spatial concentration of chiral molecules is discovered in self-aligned molecular liquids. It is shown that the interpenetration of two liquids is forming discrete diffusion barrier walls resulting in steplike concentration distribution of chiral molecules in space. The concentration gradient is at least an order of magnitude stronger from both sides of the barrier wall compared to the gradient between those walls. It is also shown that this microscopic diffusion process may be controlled by macroscopic boundary conditions imposed on the host molecular system. Both of those phenomena are related to the collective long-range orientational "elastic" interactions of molecules of the host. The observed phenomena may radically change our understanding of diffusion of chiral molecules, among others, in biological tissue, which contains many examples of self-aligned molecular liquids. This, in turn, has the potential to revolutionize drug design and delivery techniques.
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Tetrahedron Letters, 2000
A sequence of ®ve chemical steps on solid support yields hydroxy-acids in a very straightforward ... more A sequence of ®ve chemical steps on solid support yields hydroxy-acids in a very straightforward and ecient manner. The resulting compounds can be cyclized in solution phase by forming an ester bond to produce macrolactones.
Tetrahedron, 1998
A sterically unbiased macrocyclic probe has been used to study the Diels-Alder reaction mechanism... more A sterically unbiased macrocyclic probe has been used to study the Diels-Alder reaction mechanism of enal dienophiles. All the results, theoretical as well as kinetical, converge to the conclusion that a virtually non-concerted zwitterionic mechanism is possible for certain ...
Tetrahedron, 2000
The relative rate of hydrolysis of these compounds is rationalized by considering the influence o... more The relative rate of hydrolysis of these compounds is rationalized by considering the influence of steric, inductive and stereoelectronic effects on the hydrolysis reaction mechanism.
Organic Letters, 2000
When phenyl triO -benzyl-1-thio-D-galactopyranosiduronic acid esters were coupled with a 1/1 mixt... more When phenyl triO -benzyl-1-thio-D-galactopyranosiduronic acid esters were coupled with a 1/1 mixture of r and 2,3 di-O-protected D-galactopyranosiduronic acid esters, the-anomer proved to be more reactive. Data from theoretical calculations suggested that the enhanced reactivity of this anomer compared with the r one would be due to a stronger hydrogen bond of the C-4 OH with the ring oxygen.
Journal of the American Chemical Society, 1995
ABSTRACT
Crystal Growth & Design, 2009
ABSTRACT Both macrolactams cyclo-[NH−CH2−C≡C−CH2−C(Me)2-CO]n (n = 3 and n = 2) have been synthesi... more ABSTRACT Both macrolactams cyclo-[NH−CH2−C≡C−CH2−C(Me)2-CO]n (n = 3 and n = 2) have been synthesized and crystallized. They have respectively one intramolecular hydrogen bond and no such bond. Both macrocycles self-assemble as parallel supramolecular walls with or without inclusion of solvent between them. The units of the former (n = 3) are held together by NH···π/NH···OC interactions, whereas they are glued by a very dense network of classical parallel-oriented hydrogen bonds, involving all the amides of the rings, in the latter (n = 2). In that case, the bulky C(Me)2 groups are located on the surface of the walls and can be held responsible for the piling process of the layers, by means of attractive van der Waals interactions. This spatial arrangement recalls the 3D structure of cellulose, where all constitutive sheets stack mostly via van der Waals forces.
Chemistry - A European Journal, 2007
The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n... more The synthesis of four C(n) symmetric macrocyclic lactams cyclo-[NH-CH(2)-CH=CH-CH(2)-CO](n) (1, n=2; 2, n=3; 3, n=4) and cyclo-[NH-CH(2)-CH(2)-CH=CH-CO](3) (4) has been achieved by two approaches. A linear route leads to precursors that are subsequently macrocyclized in a separate step. The second, convergent approach relies on the symmetry of the targets: it includes suitably activated subunits, which are subjected to macrocyclization conditions. The subunits first oligomerize, then cyclize to form either pure macrolactams or mixtures. The macrolactam units 1, 2 and 4 stack on top each other through weak interactions (hydrogen bond and van der Waals), to form endless square, rectangular and triangular prisms, respectively. These stacks are further packed side by side in crystals grown from isotropic media. The overall dipoles in the crystals from lactams 1 and 4, which result mostly from the alignment of amide groups, are zero and large, respectively. Macrolactam 2 displays an astonishing isomorphism when allowed to cool down in anisotropic liquid crystal solutions. Large hollow hexagonal tubes are then obtained through a fractal process. Contrary to the three previous rings, 3 yields crystals where prisms of any shape are absent.
Canadian Journal of Chemistry, 2002
Transannular DielsAlder (TADA) adducts constitute a collection of rigid structures, whose confor... more Transannular DielsAlder (TADA) adducts constitute a collection of rigid structures, whose conformational diversity is rich. It is possible to design such specifically functionalized molecules capable of binding to known biological targets by molecular modelling MCSSHOOK (multiple copy simultaneous search). Here we show that such carefully designed compounds can be easily built from small synthons. TADA adducts are very interesting due to their huge conformational diversity, their rigidity (biological interest), and their ease of synthesis (chemical interest).Key words: tricycles, synthesis, transannular DielsAlder, macrocyclization, conformation, diversity.
Acta Crystallographica Section E Crystallographic Communications, 2017
The crystal structures of tert-butyl (5-chloropenta-2,4-diyn-1-yl)carbamate, C10H12ClNO2 (II), an... more The crystal structures of tert-butyl (5-chloropenta-2,4-diyn-1-yl)carbamate, C10H12ClNO2 (II), and tert-butyl (5-iodopenta-2,4-diyn-1-yl)carbamate, C10H12INO2 (IV), are isomorphous to previously reported structures and accordingly their molecular and supramolecular structures are similar. In the crystals of (II) and (IV), molecules are linked into very similar two-dimensional wall organizations with antiparallel carbamate groups involved in a combination of hydrogen and halogen bonds (bifurcated N—H...O=C and C[triple-bond]C—X...O=C interactions on the same carbonyl group). There is no long-range parallel stacking of diynes, so the topochemical polymerization of diacetylene is prevented. A Cambridge Structural Database search revealed that C[triple-bond]C—X...O=C contacts shorter than the sum of the van der Waals radii are scarce (only one structure for the C[triple-bond]C—Cl...O=C interaction and 13 structures for the similar C[triple-bond]C—I...O=C interaction).
Organic Letters, 2017
Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (D... more Given the putative selectivity of the antagonist TIPP (Tyr-Tic-Phe-Phe) for δ-opioid receptors (DOP), this compound was selected for the design of a novel 64 Cu-radiolabeled potent and selective DOP positron emission tomography (PET) imaging agent. Ex vivo autoradiography of TIPPD-PEG-K(NOTA/ 64 Cu)-NH 2 on rat brain sections produced a distribution pattern consistent with the known expression of DOP. Taken together, the in vitro and ex vivo data indicate that this 64 Cu-tracer holds promise for studying the DOP by means of PET.
Crystals, 2016
Isomorphous crystals of two diacetylene derivatives with carbamate functionality (BocNH-CH 2-diyn... more Isomorphous crystals of two diacetylene derivatives with carbamate functionality (BocNH-CH 2-diyne-X, where X = H or Br) have been obtained. The main feature of these structures is the original 2D arrangement (as supramolecular sheets or walls) in which the H bond and halogen bond have a prominent effect on the whole architecture. The two diacetylene compounds harbor neighboring carbamate (Boc protected amine) and conjugated alkyne functionalities. They differ only by the nature of the atom located at the penultimate position of the diyne moiety, either a hydrogen atom or a bromine atom. Both of them adopt very similar 2D wall organizations with antiparallel carbamates (as in antiparallel beta pleated sheets). Additional weak interactions inside the same walls between molecular bricks are H bond interactions (diyne-H¨¨¨O=C) or halogen bond interactions (diyne-Br¨¨¨O=C), respectively. Based on crystallographic atom coordinates, DFT (B3LYP/6-31++G(d,p)) and DFT (M06-2X/6-31++G(d,p)) calculations were performed on these isostructural crystals to gain insight into the intermolecular interactions.
Tetrahedron, 1998
Various 14-membered macrocyclic trienes underwent transannular Diels-Alder reactions to yield tet... more Various 14-membered macrocyclic trienes underwent transannular Diels-Alder reactions to yield tetracyclic structures that are stereoisomers of steroids. Due to the complexity of the effects at work during these reactions, a thorough molecular modeling study was carried out. Thus, some molecular mechanics, semiempirical and ab initio methods were compared and the results were finally used to rationalize the experimental results.
Peptides Across the Pacific: The Proceedings of the Twenty-Third American and the Sixth International Peptide Symposium, 2013
We extend to you a warm and sunny Aloha in celebration of the 23 rd American Peptide Symposium an... more We extend to you a warm and sunny Aloha in celebration of the 23 rd American Peptide Symposium and the 6 th International Symposium. The meeting theme, Peptides Across the Pacific, embraced the spirit of the scientific and social program. Peptides Across the Pacific encompassed the important role that peptide science currently plays in so many disciplines and explored the potential impact peptides can make in scientific fields that have yet to realize the utility of these wonderful molecules. The scientific program for 2013 was framed by distinguished lectures delivered by two renowned peptide chemists.