Selective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated S_NAr Reactions

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

SNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with neighboring Lys residue model small peptides. Such self-activation ascribed to stronger electron-withdrawing capability respect that parent aldehyde stabilized transition state reaction, together higher preorganization reactive groups in cationic aldiminium species. This approach further applied for functionalization two antibodies. In both cases, presence group close proximity resulted noteworthy increase bioconjugation yields, excellent chemo-selectivity. Whereas modification an IgG1 antibody led stochastic product distributions, microenvironment selectivity noted when employing IgG4, line lower number residues hinge region latter. Additionally, postfunctionalization modified antibodies attained through exchange tethered derivative hydrazides, representing unprecedented "tag modify" selective strategy DCvC.

Language: Английский

Imine based covalent adaptable networks from diacetone acrylamide polymerization

Published: Oct. 17, 2024

The construction of covalent adaptable networks (CANs) without the need for post-modification, complex monomer synthesis routes, or expensive materials is highly desirable practical application dynamic chemistry. In present study, commercially available acrylate monomer, diacetone acrylamide (DAAM), was initially polymerized using a traditional radical polymerization method. Subsequently, it cross-linked with amine agents under hot-processing conditions to form aliphatic imine-based CANs. resulting exhibited glass transition temperatures (T_g) in range 95 107°C, good thermal stability, mechanical and thermomechanical properties. All samples were amenable recycling. Post-recycling, both tensile strength Young's Modulus slight deterioration, retaining approximately 80% their original results from gel content analysis structural characterization pristine recycled indicate that observed reduction properties T_g (approximately 70°C) can be attributed decrease degree cross-linking release ketone groups. Furthermore, all demonstrated degradability acidic conditions, attributable imine structure. By this facile approach prepare acrylate-based CANs, we establish an important framework polymer are reprocessable biodegradable.

Language: Английский

Feedback driven autonomous cycles of assembly and disassembly from minimal building blocks

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 18, 2024

The construction of complex systems by simple chemicals that can display emergent network dynamics might contribute to our understanding behavior from organic reactions. Here we design single amino acid/dipeptide-based exhibit multiple periodic changes (dis)assembly under non-equilibrium conditions in closed system, importantly the absence evolved biocatalysts. two-component based building block exploits pH driven non-covalent assembly and time-delayed accelerated catalysis self-assembled state install orthogonal feedback loops with a batch reactants. Mathematical modelling reaction establishes oscillations are transient for this structure helps predict relative contribution loop ability system such oscillation. Such autonomous purely synthetic molecules starting point enable active materials properties. study formed Here, built on minimal blocks, authors describe utilizing controlled pH-driven assembly.

Language: Английский