Biomimetic asymmetric catalysis based on biological and synthetic macromolecular scaffolds

Gedurende de laatste decennia zijn er grote inspanningen verricht door chemici om replicas van enzymen te ontwerpen en fabriceren die zijn gebaseerd op verschillende macromoleculaire templates. Deze macromoleculen kunnen worden verdeeld in twee groepen: biologische platformen (eiwitten, peptiden en nucleotiden) en synthetische holtes met hydrofobe bindplaatsen. Kandidaten uit beide klasses kunnen een combinatie van interacties bieden (waterstof bruggen, π-π stapeling, electrostatische en hydrofobe interacties) aan het substraat, de overgangstoestand en het metaal complex. Daarom worden de macromoleculaire componenten rondom het metaal centrum gedefinierd als de tweede cöordinatie sfeer. Dit uitgebreide scala aan mogelijkheden heeft nieuwe reactiviteit en selectiviteit aan verschillende belangrijke organische reacties gebracht.Dit proefschrift betrekking op het ontwerp van nieuwe biomimetische katalytische systemen en deze toegepast asymmetrische katalysatoren voor verschillende chemische reacties

Biomimetic asymmetric catalysis based on biological and synthetic macromolecular scaffolds

Gedurende de laatste decennia zijn er grote inspanningen verricht door chemici om replicas van enzymen te ontwerpen en fabriceren die zijn gebaseerd op verschillende macromoleculaire templates. Deze macromoleculen kunnen worden verdeeld in twee groepen: biologische platformen (eiwitten, peptiden en nucleotiden) en synthetische holtes met hydrofobe bindplaatsen. Kandidaten uit beide klasses kunnen een combinatie van interacties bieden (waterstof bruggen, π-π stapeling, electrostatische en hydrofobe interacties) aan het substraat, de overgangstoestand en het metaal complex. Daarom worden de macromoleculaire componenten rondom het metaal centrum gedefinierd als de tweede cöordinatie sfeer. Dit uitgebreide scala aan mogelijkheden heeft nieuwe reactiviteit en selectiviteit aan verschillende belangrijke organische reacties gebracht.Dit proefschrift betrekking op het ontwerp van nieuwe biomimetische katalytische systemen en deze toegepast asymmetrische katalysatoren voor verschillende chemische reacties

MemoryCompanion: A Smart Healthcare Solution to Empower Efficient Alzheimer's Care Via Unleashing Generative AI

With the rise of Large Language Models (LLMs), notably characterized by GPT frameworks, there emerges a catalyst for novel healthcare applications. Earlier iterations of chatbot caregivers, though existent, have yet to achieve a dimension of human-like authenticity. This paper unveils `MemoryCompanion' a pioneering digital health solution explicitly tailored for Alzheimer's disease (AD) patients and their caregivers. Drawing upon the nuances of GPT technology and prompt engineering, MemoryCompanion manifests a personalized caregiving paradigm, fostering interactions via voice-cloning and talking-face mechanisms that resonate with the familiarity of known companions. Using advanced prompt-engineering, the system intricately adapts to each patient's distinct profile, curating its content and communication style accordingly. This approach strives to counteract prevalent issues of social isolation and loneliness frequently observed in AD demographics. Our methodology, grounded in its innovative design, addresses both the caregiving and technological challenges intrinsic to this domain

Fracture Detection in Bio-Glues with Fluorescent-Protein-Based Optical Force Probes

Glues are being used to bond, seal, and repair in industry and biomedicine. The improvement of gluing performance is hence important for the development of new glues with better and balanced property spaces, which in turn necessitates a mechanistic understanding of their mechanical failure. Optical force probes (OFPs) allow the observation of mechanical material damage in polymers from the macro- down to the microscale, yet have never been employed in glues. Here, the development of a series of ratiometric OFPs based on fluorescent-protein–dye and protein–protein conjugates and their incorporation into genetically engineered bio-glues is reported. The OFPs are designed to efficiently modulate Förster resonance energy transfer upon force application thereby reporting on force-induced molecular alterations independent of concentration and fluorescence intensity both spectrally and through their fluorescence lifetime. By fluorescence spectroscopy in solution and in the solid state and by fluorescence lifetime imaging microscopy, stress concentrations are visualized and adhesive and cohesive failure in the fracture zone is differentiated.</p

Photochemical control of bacterial gene expression based ontransencoded genetic switches

Controlling gene expression by light with fine spatiotemporal resolution not only allows understanding and manipulating fundamental biological processes but also fuels the development of novel therapeutic strategies. In complement to exploiting optogenetic tools, photochemical strategies mostly rely on the incorporation of photo-responsive small molecules into the corresponding biomacromolecular scaffolds. Therefore, generally large synthetic effort is required and the switching of gene expression in both directions within a single system remains a challenge. Here, we report a trans encoded ribo-switch, which consists of an engineered tRNA mimicking structure (TMS), under control of small photo-switchable signalling molecules. The signalling molecules consist of two amino glycoside molecules that are connected via an azobenzene unit. The light responsiveness of our system originates from the photo-switchable noncovalent interactions between the signalling molecule and the TMS switch, leading to the demonstration of photochemically controlled expression of two different genes. We believe that this modular design will provide a powerful platform for controlling the expression of other functional proteins with high spatiotemporal resolution employing light as a stimulus

Efficient Commitment to Functional CD34+ Progenitor Cells from Human Bone Marrow Mesenchymal Stem-Cell-Derived Induced Pluripotent Stem Cells

The efficient commitment of a specialized cell type from induced pluripotent stem cells (iPSCs) without contamination from unknown substances is crucial to their use in clinical applications. Here, we propose that CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential, could be efficiently obtained from iPSCs derived from human bone marrow mesenchymal stem cells (hBMMSC-iPSCs) with defined factors. By treatment with a cocktail containing mesodermal, hematopoietic, and endothelial inducers (BMP4, SCF, and VEGF, respectively) for 5 days, hBMMSC-iPSCs expressed the mesodermal transcription factors Brachyury and GATA-2 at higher levels than untreated groups (P<0.05). After culturing with another hematopoietic and endothelial inducer cocktail, including SCF, Flt3L, VEGF and IL-3, for an additional 7–9 days, CD34+ progenitor cells, which were undetectable in the initial iPSC cultures, reached nearly 20% of the total culture. This was greater than the relative number of progenitor cells produced from human-skin-fibroblast-derived iPSCs (hFib-iPSCs) or from the spontaneous differentiation groups (P<0.05), as assessed by flow cytometry analysis. These induced cells expressed hematopoietic transcription factors TAL-1 and SCL. They developed into various hematopoietic colonies when exposed to semisolid media with hematopoietic cytokines such as EPO and G-CSF. Hematopoietic cell lineages were identified by phenotype analysis with Wright-Giemsa staining. The endothelial potential of the cells was also verified by the confirmation of the formation of vascular tube-like structures and the expression of endothelial-specific markers CD31 and VE-CADHERIN. Efficient induction of CD34+ progenitor cells, which retain hematopoietic and endothelial cell potential with defined factors, provides an opportunity to obtain patient-specific cells for iPSC therapy and a useful model for the study of the mechanisms of hematopoiesis and drug screening