alpha,beta-Unsaturated 2-Acyl-Imidazoles in Asymmetric Biohybrid Catalysis

International audienceα,β‐Unsaturated acylimidazoles have been used in a plethora of enantioselective transformations over the years and have unsurprisingly become privileged building blocks for asymmetric catalysis. Interestingly however, their use in asymmetric biohybrid catalysis as bidentate substrates able to interact with artificial metalloenzymes has only recently emerged, expanding considerably in the last few years. Easy to prepare and to post‐transform, α,β‐unsaturated acylimidazoles appear as leading synthons for the asymmetric construction of C−C and C−O bonds. This Minireview highlights the current and increasing interest of these key building blocks in the context of asymmetric biohybrid catalysis with the aim to stimulate further research into their still unexploited potential. The use of these α,β‐unsaturated acylimidazoles in metal‐catalyzed and organocatalyzed transformations will be covered in a back‐to‐back Minireview by Renata Marcia de Figueiredo, Jean‐Marc Campagne and co‐workers

A decade of DNA-hybrid catalysis: from innovation to comprehension

crosscheck: This document is CrossCheck deposited identifier: Michael Smietana (ORCID) identifier: Stellios Arseniyadis (ORCID) identifier: Stellios Arseniyadis (ResearcherID) copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal history: Received 22 January 2017; Accepted 23 April 2017; Accepted Manuscript published 25 April 2017; Advance Article published 9 May 2017We would like to thank the Agence Nationale de la Recherche for funding – the NCiS project (ANR-2010-JCJC-715-1) and the D-CYSIV project (ANR-2015-CE29-0021-01

DNA-Based Asymmetric Inverse Electron-Demand Hetero-Diels-Alder

International audienceWhile artificial cyclases hold great promise in chemical synthesis, this work presents the first example of a DNA-catalyzed inverse electron-demand hetero-Diels-Alder (IEDHDA) between dihydrofuran and various α,β-unsaturated acyl imidazoles. The resulting fused bicyclic O,O-acetals containing three contiguous stereogenic centers are obtained in high yields (up to 99 %) and excellent diastereo- (up to >99:1 dr) and enantioselectivities (up to 95 % ee) using a low catalyst loading. Most importantly, these results show that the concept of DNA-based asymmetric catalysis can be expanded to new synthetic transformations offering an efficient, sustainable, and highly selective tool for the construction of chiral building blocks

DNA-cellulose: an economical, fully recyclable and highly effective chiral biomaterial for asymmetric catalysis

similarity_check: This document is Similarity Check deposited related_data: Supplementary Information copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal peer_review_method: Single-blind history: Received 20 December 2014; Accepted 11 January 2015; Accepted Manuscript published 14 January 2015; Advance Article published 23 January 2015; Version of Record published 24 March 2015This research was supported by the Ministe`re de l’Enseignement Supe´rieur et de la Recherche and the Agence Nationale de la Recherche (NCiS; ANR-2010-JCJC-715-1)

Allogeneic Versus Autologous Derived Cell Sources for Use in Engineered Bone-Ligament-Bone Grafts in Sheep Anterior Cruciate Ligament Repair

The use of autografts versus allografts for anterior cruciate ligament (ACL) reconstruction is controversial. The current popular options for ACL reconstruction are patellar tendon or hamstring autografts, yet advances in allograft technologies have made allogeneic grafts a favorable option for repair tissue. Despite this, the mismatched biomechanical properties and risk of osteoarthritis resulting from the current graft technologies have prompted the investigation of new tissue sources for ACL reconstruction. Previous work by our lab has demonstrated that tissue-engineered bone-ligament-bone (BLB) constructs generated from an allogeneic cell source develop structural and functional properties similar to those of native ACL and vascular and neural structures that exceed those of autologous patellar tendon grafts. In this study, we investigated the effectiveness of our tissue-engineered ligament constructs fabricated from autologous versus allogeneic cell sources. Our preliminary results demonstrate that 6 months postimplantation, our tissue-engineered auto- and allogeneic BLB grafts show similar histological and mechanical outcomes indicating that the autologous grafts are a viable option for ACL reconstruction. These data indicate that our tissue-engineered autologous ligament graft could be used in clinical situations where immune rejection and disease transmission may preclude allograft use.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140234/1/ten.tea.2014.0422.pd

Fresh Versus Frozen Engineered Bone–Ligament–Bone Grafts for Sheep Anterior Cruciate Ligament Repair

Surgical intervention is often required to restore knee instability in patients with anterior cruciate ligament (ACL) injury. The most commonly used grafts for ACL reconstruction are tendon autografts or allografts. These current options, however, have shown failure rates requiring revision and continued instability in the long term. The mismatched biomechanical properties of the current tendon grafts compared with native ACL tissue are thought to contribute to these poor outcomes and potential risk of early onset osteoarthritis. As a possible solution to these issues, our laboratory has fabricated tissue-engineered ligament constructs that exhibit structural and functional properties similar to those of native ACL tissue after 6 months implantation. In addition, these tissue-engineered grafts achieve vascular and neural development that exceeds those of patellar tendon grafts. However, the utility of our tissue-engineered grafts is limited by the labor-intensive method required to produce the constructs and the need to use the constructs fresh, directly from the cell culturing system. Ideally, these constructs would be fabricated and stored until needed. Thus, in this study, we investigated the efficacy of freezing our tissue-engineered constructs as a method of preservation before use for ACL reconstruction. We hypothesized that frozen constructs would have similar histological and biomechanical outcomes compared with our fresh model. Our results showed that 6 months postimplantation as an ACL replacement graft, both our tissue-engineered fresh and frozen grafts demonstrated similar mechanical and histological outcomes, indicating that freezing is a suitable method for preserving and storing our graft before ACL reconstruction. The ability to use frozen constructs significantly increases the versatility of our graft technology expanding the clinical utility of our graft.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140250/1/ten.tec.2014.0542.pd

Charge-transfer interactions stabilize g-quadruplex-forming thrombin binding aptamers and can improve their anticoagulant activity

In the search for optimized thrombin binding aptamers (TBAs), we herein describe the synthesis of a library of TBA analogues obtained by end-functionalization with the electron-rich 1,5-dialkoxy naphthalene (DAN) and the electron-deficient 1,8,4,5-naphthalenetetra-carboxylic diimide (NDI) moieties. Indeed, when these G-rich oligonucleotides were folded into the peculiar TBA G-quadruplex (G4) structure, effective donor–acceptor charge transfer interactions between the DAN and NDI residues attached to the extremities of the sequence were induced, providing pseudo-cyclic structures. Alternatively, insertion of NDI groups at both extremities produced TBA analogues stabilized by π–π stacking interactions. All the doubly-modified TBAs were characterized by different biophysical techniques and compared with the analogues carrying only the DAN or NDI residue and unmodified TBA. These modified TBAs exhibited higher nuclease resistance, and their G4 structures were markedly stabilized, as evidenced by increased Tm values compared to TBA. These favorable properties were also associated with improved anticoagulant activity for one DAN/NDI-modified TBA, and for one NDI/NDI-modified TBA. Our results indicated that TBA pseudo-cyclic structuring by ad hoc designed end-functionalization represents an efficient approach to improve the aptamer features, while pre-organizing and stabilizing the G4 structure but allowing sufficient flexibility to the aptamer folding, which is necessary for optimal thrombin recognition

Three-Dimensional Engineered Bone–Ligament–Bone Constructs for Anterior Cruciate Ligament Replacement

The anterior cruciate ligament (ACL), a major stabilizer of the knee, is commonly injured. Because of its intrinsic poor healing ability, a torn ACL is usually reconstructed by a graft. We developed a multi-phasic, or bone?ligament?bone, tissue-engineered construct for ACL grafts using bone marrow stromal cells and sheep as a model system. After 6 months in vivo, the constructs increased in cross section and exhibited a well-organized microstructure, native bone integration, a functional enthesis, vascularization, innervation, increased collagen content, and structural alignment. The constructs increased in stiffness to 52% of the tangent modulus and 95% of the geometric stiffness of native ACL. The viscoelastic response of the explants was virtually indistinguishable from that of adult ACL. These results suggest that our constructs after implantation can obtain physiologically relevant structural and functional characteristics comparable to those of adult ACL. They present a viable option for ACL replacement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98477/1/ten%2Etea%2E2011%2E0231.pd

Wide-field time-correlated single photon counting-based fluorescence lifetime imaging microscopy

Wide-field time-correlated single photon counting detection techniques, where the position and the arrival time of the photons are recorded simultaneously using a camera, have made some advances recently. The technology and instrumentation used for this approach is employed in areas such as nuclear science, mass spectroscopy and positron emission tomography, but here, we discuss some of the wide-field TCSPC methods, for applications in fluorescence microscopy. We describe work by us and others as presented in the Ulitima fast imaging and tracking conference at the Argonne National Laboratory in September 2018, from phosphorescence lifetime imaging (PLIM) microscopy on the microsecond time scale to fluorescence lifetime imaging (FLIM) on the nanosecond time scale, and highlight some applications of these techniques