Nitrones are key intermediates in organic synthesis and the pharmaceutical industry. The heterogeneous synthesis of nitrones with multifunctional catalysts is extremely attractive but rarely explored. Herein, we report ultrasmall platinum nanoclusters (PtNCs) encapsulated in amine-functionalized Zr metal-organic framework (MOF), UiO-66-NH (Pt@UiO-66-NH ) as a multifunctional catalyst in the one-pot tandem synthesis of nitrones. By virtue of the cooperative interplay among the selective hydrogenation activity provided by the ultrasmall PtNCs and Lewis acidity/basicity/nanoconfinement endowed by UiO-66-NH , Pt@UiO-66-NH exhibits remarkable activity and selectivity, in comparison to Pt/carbon, Pt@UiO-66, and Pd@UiO-66-NH . Pt@UiO-66-NH also outperforms Pt nanoparticles supported on the external surface of the same MOF (Pt/UiO-66-NH ). To our knowledge, this work demonstrates the first examples of one-pot synthesis of nitrones using recyclable multifunctional heterogeneous catalysts.
H-NS proteins act as osmotic sensors translating changes in osmolarity into altered DNA binding properties, thus, regulating enterobacterial genome organization and genes transcription. The molecular mechanism underlying the switching process and its conservation among H-NS family members remains elusive.Here, we focus on the H-NS family protein MvaT from P. aeruginosa and demonstrate experimentally that its protomer exists in two different conformations, corresponding to two different functional states. In the half-opened state (dominant at low salt) the protein forms filaments along DNA, in the fully opened state (dominant at high salt) the protein bridges DNA. This switching is a direct effect of ionic strengths on electrostatic interactions between the appositively charged DNA binding and N-terminal domains of MvaT. The asymmetric charge distribution and intramolecular interactions are conserved among the H-NS family of proteins. Therefore, our study establishes a general paradigm for the molecular mechanistic basis of the osmosensitivity of H-NS proteins.
Protein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce novel and broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse Nanobodies that either stabilize or disrupt PPIs in a single experiment. We applied ChILL and DisCO to identify competitive, connective or fully allosteric Nanobodies that inhibit or facilitate the formation of the SOS1-RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro and RAS signalling in cellulo. One of these connective Nanobodies fills a cavity that was previously identified as the binding pocket for a series of therapeutic lead compounds. The long complementarity-determining region (CDR3) that penetrates this binding pocket serves as an innovative pharmacophore for extending the repertoire of potential leads.
The library of imine-linked covalent organic frameworks
(COFs)
has grown significantly over the last two decades, featuring a variety
of morphologies, pore sizes, and applications. An array of synthetic
methods has been developed to expand the scope of the COF functionalities;
however, most of these methods were designed to introduce functional
scaffolds tailored to a specific application. Having a general approach
to diversify COFs via late-stage incorporation of functional group
handles would greatly facilitate the transformation of these materials
into platforms for a variety of useful applications. Herein, we report
a general strategy to introduce functional group handles in COFs via
the Ugi multicomponent reaction. To demonstrate the versatility of
this approach, we have synthesized two COFs with hexagonal and kagome
morphologies. We then introduced azide, alkyne, and vinyl functional
groups, which could be readily utilized for a variety of post-synthetic
modifications. This facile approach enables the functionalization
of any COFs containing imine linkages.
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