Active droplets through enzyme-free, dynamic phosphorylation DOI Creative Commons
Simone Poprawa, Michele Stasi, Monika Wenisch

и другие.

Опубликована: Дек. 28, 2023

Life continuously transduces energy to perform critical functions using stored in reactive molecules like ATP or NADH. dynamically phosphorylates active sites on proteins and thereby regulates their function. Inspired by such machinery, regulating supramolecular has gained traction. Enzyme-free, synthetic systems that use dynamic phosphorylation regulate processes do not exist. We present an enzyme-free reaction cycle consumes phosphorylating agents transiently amino acids. The phosphorylated acids are labile deactivate through hydrolysis. exhibits versatility tunability, allowing for the of multiple precursors with a tunable half-life. Notably, we show resulting products can peptide’s phase separation, leading droplets require continuous conversion fuel sustain. Our new will be valuable as model biological but also offer insights into protocell formation.

Язык: Английский

Photoswitchable Imines Drive Dynamic Covalent Systems to Nonequilibrium Steady States DOI Creative Commons
Jiarong Wu, Jake L. Greenfield

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(30), С. 20720 - 20727

Опубликована: Июль 18, 2024

Coupling a photochemical reaction to thermal exchange process can drive the latter nonequilibrium steady state (NESS) under photoirradiation. Typically, systems use separate motifs for photoresponse and equilibrium-related processes. Here, we show that photoswitchable imines fulfill both roles simultaneously, autonomously driving dynamic covalent system into NESS continuous light irradiation. We demonstrate this using transimination reactions, where

Язык: Английский

Процитировано

11
Active droplets through enzyme-free, dynamic phosphorylation DOI Creative Commons
Simone Poprawa, Michele Stasi, Brigitte A. K. Kriebisch

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Май 17, 2024

Abstract Life continuously transduces energy to perform critical functions using stored in reactive molecules like ATP or NADH. dynamically phosphorylates active sites on proteins and thereby regulates their function. Inspired by such machinery, regulating supramolecular has gained traction. Enzyme-free, synthetic systems that use dynamic phosphorylation regulate processes have not yet been reported, our knowledge. Here, we show an enzyme-free reaction cycle consumes the phosphorylating agent monoamidophosphate transiently histidine histidine-containing peptides. The phosphorylated species are labile deactivate through hydrolysis. exhibits versatility tunability, allowing for of multiple precursors with a tunable half-life. Notably, resulting products can peptide’s phase separation, leading droplets require continuous conversion fuel sustain. will be valuable as model biological but also offer insights into protocell formation.

Язык: Английский

Процитировано

9
Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels DOI Creative Commons
Mahesh D. Pol, Kun Dai, Ralf Thomann

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(28)

Опубликована: Апрель 27, 2024

Abstract Despite great progress in the construction of non‐equilibrium systems, most approaches do not consider structure fuel as a critical element to control processes. Herein, we show that amino acid side chains (A, F, Nal) abiotic phosphates can direct assembly and reactivity during transient formation. The fuels bind covalently substrates subsequently influence structures process. We focus on ways which phosphate esters guide formation how cross regulate when constructing assemblies. Through chemical functionalization energy‐rich aminoacyl esters, are able yield thioesters upon adding dipeptides containing tyrosine or cysteine residues. structural elements around lifetime formed their supramolecular These properties be further influenced by peptide sequence substrates, incorporating anionic, aliphatic aromatic Furthermore, illustrate oligomerization initiated from single ester residue (Y). findings suggest activated acids with varying energy contents pave way for designing fabricating structured fuels.

Язык: Английский

Процитировано

7
Selective peptide bond formation via side chain reactivity and self-assembly of abiotic phosphates DOI Creative Commons
Arti Sharma, Kun Dai, Mahesh D. Pol

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 3, 2025

Abstract In the realm of biology, peptide bonds are formed via reactive phosphate-containing intermediates, facilitated by compartmentalized environments that ensure precise coupling and folding. Herein, we use aminoacyl phosphate esters, synthetic counterparts biological adenylates, drive selective bond formation through side chain-controlled reactivity self-assembly. This strategy results in preferential incorporation positively charged amino acids from mixtures containing natural non-natural during spontaneous amide water. Conversely, esters lack assembly exhibit fast result random coupling. By introducing structural modifications to (ethyl vs . phenyl) while retaining aggregation, able tune selectivity incorporating aromatic acid residues. approach enables synthesis sequences tailored specific overcoming limitations posed certain combinations. Furthermore, demonstrate a balance between electrostatic stacking interactions facilitates covalent self-sorting or co-assembly oligomerization reactions using unprotected N-terminus esters. These findings suggest self-assembly abiotic can activate selection mechanism enabling departure randomness autonomous

Язык: Английский

Процитировано

0
Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels DOI Creative Commons
Mahesh D. Pol, Kun Dai, Ralf Thomann

и другие.

Angewandte Chemie, Год журнала: 2024, Номер 136(28)

Опубликована: Апрель 27, 2024

Abstract Despite great progress in the construction of non‐equilibrium systems, most approaches do not consider structure fuel as a critical element to control processes. Herein, we show that amino acid side chains (A, F, Nal) abiotic phosphates can direct assembly and reactivity during transient formation. The fuels bind covalently substrates subsequently influence structures process. We focus on ways which phosphate esters guide formation how cross regulate when constructing assemblies. Through chemical functionalization energy‐rich aminoacyl esters, are able yield thioesters upon adding dipeptides containing tyrosine or cysteine residues. structural elements around lifetime formed their supramolecular These properties be further influenced by peptide sequence substrates, incorporating anionic, aliphatic aromatic Furthermore, illustrate oligomerization initiated from single ester residue (Y). findings suggest activated acids with varying energy contents pave way for designing fabricating structured fuels.

Язык: Английский

Процитировано

3
Allosteric Control of the Catalytic Properties of Dipeptide-Based Supramolecular Assemblies DOI
Soumili Roy,

Janmejay Laha,

Antara Reja

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22522 - 22529

Опубликована: Авг. 1, 2024

Allostery, as seen in extant biology, governs the activity regulation of enzymes through redistribution conformational equilibria upon binding an effector. Herein, a minimal design is demonstrated where dipeptide can exploit dynamic imine linkage to condense with simple aldehydes access spherical aggregates catalytically active states, which facilitates orthogonal reaction due closer proximity catalytic residues (imidazoles). The allosteric site (amine) catalyst concomitantly bind inhibitor via exchange, leads alternation energy landscape self-assembled state, resulting downregulation activity. Further, temporal control over realized feedback-controlled autonomous network that utilizes hydrolytic (in)active state function time.

Язык: Английский

Процитировано

3
Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly DOI Creative Commons
Mahesh D. Pol, Ralf Thomann, Yi Thomann

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(43), С. 29621 - 29629

Опубликована: Окт. 17, 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 cascade reactions in aqueous media remains challenging due need control multiple, sequential a single pot manage stability reactive intermediates. Herein, we developed abiotic cascades 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 undergo hydrolysis, bypassing transformations after thioester formation. Additionally, mixtures containing multiple substrates, achieved selective product following distinct pathway favors subsequent through changes self-assembly. By coupling with molecules varying time scales, reaction clocks lifetimes dynamics, facilitating precise temporal regulation.

Язык: Английский

Процитировано

3
Biomolecular Condensates: From Bacterial Compartments to Incubator Spaces of Emergent Chemical Systems in Matter‐to‐Life Transitions DOI Creative Commons

Wade E. Schnorr,

W. Seth Childers

ChemSystemsChem, Год журнала: 2024, Номер 6(4)

Опубликована: Апрель 17, 2024

Abstract At the earliest development of prebiotic chemistry, bacterial cells were primarily viewed as “bags molecules.” This longstanding viewpoint shaped and biased early research about life's origins, setting an initial target when considering path from chemistry to modern life. The two fields systems cell biology seem like oil water, but each brings their own perspectives methods consider “what is life?”. Here, we review most recent discoveries in biology, focusing on biomolecular condensates how they may impact our thinking matter‐to‐life transitions. presence condensate compartments domain life strengthens hypothesis that play roles coordinating chemical origins. Bacterial have been shown enhance enzymatic reactions, tune substrate specificity, be responsive environmental conditions metabolites. Systems studies further illuminated unique environment within strategies for logically tying processes formation dissolution condensates. We potential provide “incubator spaces” where new chemistries can develop examine future challenges regarding capability yield emergent capable selection.

Язык: Английский

Процитировано

2
Active droplets through enzyme-free, dynamic phosphorylation DOI Creative Commons
Job Boekhoven, Simone Poprawa, Michele Stasi

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Янв. 8, 2024

Abstract Life continuously transduces energy to perform critical functions using stored in reactive molecules like ATP or NADH. dynamically phosphorylates active sites on proteins and thereby regulates their function. Inspired by such machinery, regulating supramolecular has gained traction. Enzyme-free, synthetic systems that use dynamic phosphorylation regulate processes do not exist. We present an enzyme-free reaction cycle consumes phosphorylating agents transiently amino acids. The phosphorylated acids are labile deactivate through hydrolysis. exhibits versatility tunability, allowing for the of multiple precursors with a tunable half-life. Notably, we show resulting products can peptide’s phase separation, leading droplets require continuous conversion fuel sustain. Our new will be valuable as model biological but also offer insights into protocell formation.

Язык: Английский

Процитировано

1
Abiotic Acyl Transfer Cascades Driven by Aminoacyl Phosphate Esters and Self-Assembly DOI Creative Commons

Mahesh Pol,

Ralf Thomann, Yi Thomann

и другие.

Опубликована: Авг. 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.

Язык: Английский

Процитировано

1