Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly DOI Creative Commons

Mahesh Pol,

Ralf Thomann, Yi Thomann

et al.

Published: Aug. 5, 2024

Biochemical acyl transfer cascades, such as those initiated by the adenylation of carboxylic acids, are central to various biological processes, including protein synthesis and fatty acid metabolism. Designing aqueous cascades outside biology remains challenging due need control multiple, sequential reactions in a single pot manage stability reactive intermediates. Herein, we developed abiotic using aminoacyl phosphate esters, synthetic counterparts adenylates, drive chemical self-assembly pot. We demonstrated that structural elements amino side chains (aromatic versus aliphatic) significantly influence reactivity half-lives ranging from hours days. This behavior, turn, affects number couplings can achieve network propensity activated intermediate structures. The constructed bifunctional peptide substrates featuring chain nucleophiles. Specifically, aromatic acids facilitate formation transient thioesters, which preorganized into spherical aggregates further couple chimeric assemblies composed esters thioesters. In contrast, aliphatic lack ability form structures, predominantly lead hydrolysis, bypassing elongation after thioester formation. Additionally, mixtures containing multiple substrates, achieved selective product following distinct pathway favors through self-assembly. By coupling molecules with varying timescales, reaction clocks lifetimes dynamics, thereby facilitating precise temporal regulation.

Language: Английский

Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly DOI Creative Commons

Mahesh Pol,

Ralf Thomann, Yi Thomann

et al.

Published: Aug. 5, 2024

Biochemical acyl transfer cascades, such as those initiated by the adenylation of carboxylic acids, are central to various biological processes, including protein synthesis and fatty acid metabolism. Designing aqueous cascades outside biology remains challenging due need control multiple, sequential reactions in a single pot manage stability reactive intermediates. Herein, we developed abiotic using aminoacyl phosphate esters, synthetic counterparts adenylates, drive chemical self-assembly pot. We demonstrated that structural elements amino side chains (aromatic versus aliphatic) significantly influence reactivity half-lives ranging from hours days. This behavior, turn, affects number couplings can achieve network propensity activated intermediate structures. The constructed bifunctional peptide substrates featuring chain nucleophiles. Specifically, aromatic acids facilitate formation transient thioesters, which preorganized into spherical aggregates further couple chimeric assemblies composed esters thioesters. In contrast, aliphatic lack ability form structures, predominantly lead hydrolysis, bypassing elongation after thioester formation. Additionally, mixtures containing multiple substrates, achieved selective product following distinct pathway favors through self-assembly. By coupling molecules with varying timescales, reaction clocks lifetimes dynamics, thereby facilitating precise temporal regulation.

Language: Английский

Citations

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