Spontaneous and Selective Peptide Elongation in Water Driven by Aminoacyl Phosphate Esters and Phase Changes

Dai, Kun; Pol, Mahesh D.; Saile, Lenard; Sharma, Arti; Liu, Bin; Thomann, Ralf; Trefs, Johanna L.; Qiu, Danye; Moser, Sandra; Wiesler, Stefan; Balzer, Bizan N.; Hugel, Thorsten; Jessen, Henning J.; Pappas, Charalampos G.

doi:10.1021/jacs.3c07918

Cited by 17 publications

(7 citation statements)

References 63 publications

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“…We previously demonstrated that aminoacyl phosphate esters can be utilized for the spontaneous and selective oligomerization of peptide bonds in water, where the hydrophobicity in the structure of monomers dictates the length of the oligomerization and the composition in different phases. 33 Herein, we focus on designing activated molecules, which can impact non-equilibrium processes. Thus, we design systems considering the ways in which activated molecules can: 1) incorporate structural elements in their structure but are not capable of pre-organization, 2) guide structure formation upon transferring energy and reactivity into other species and 3) interact with various substrates (peptide nucleophiles), which can further alter the pathway and contribute to the assembly process up coupling.…”

Section: Resultsmentioning

confidence: 99%

Guiding Transient Peptide Assemblies with Structural Elements Around Abiotic Phosphate Fuels

Pappas,

Pol,

Dai

et al. 2023

Preprint

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Biochemical energy carriers, such as triphosphates (ATP, GTP) drive selective processes, by incorporating chemical information (Adenine vs. Guanine) in their structure. These recognition elements match with complex machineries through a variety of non-covalent interactions, enabling specific targeting of functions. In contrast, most approaches in non-equilibrium systems do not consider the structure of the fuel as a critical element to control the processes. Herein, we show that the amino acid side chains (A, F, Nap) in the structure of activated aminoacyl phosphate esters can direct assembly and reactivity in the context of non-equilibrium structure formation. We focus on the ways in which the activated amino acids guide structure formation and how structures and reactivity cross regulate when constructing different assemblies. Through the chemical functionalization of energy-rich aminoacyl phosphate esters, we are able to control the coupling yield to esters and thioesters upon adding dipeptides containing tyrosine or cysteine amino acid residues. The structural elements around the phosphate esters guide the lifetime of the structures formed and their supramolecular assemblies, which can further be influenced by the structure and reactivity of dipeptide substrates. Moreover, we demonstrate that an aminoacyl phosphate ester incorporating a tyrosine residue (Y) can autonomously generate a pool of high energy molecules, where dynamic oligomerization and de-oligomerization of esters occurs in a single step process. These findings suggest that activated amino acids with varying reactivity and energy contents can pave the way for designing and fabricating structured fuels

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Section: Resultsmentioning

confidence: 99%

Guiding Transient Peptide Assemblies with Structural Elements Around Abiotic Phosphate Fuels

Pappas,

Pol,

Dai

et al. 2023

Preprint

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show abstract

“…We previously demonstrated that aminoacyl phosphate esters can be utilized for the spontaneous and selective oligomerization of peptide bonds in water, where the hydrophobicity in the structure of monomers dictates the length of the oligomerization and the composition in different phases. [41] Herein, we focused on designing activated molecules, which can impact non-equilibrium processes. Thus, we designed systems considering the ways in which activated molecules can: 1) incorporate structural elements in their structure but are not capable of pre-organization and 2) bind covalently to substrates and subsequently influence the structures in the assembly process.…”

Section: Covalent Binding Of Fuels To Substratesmentioning

confidence: 99%

“…The authors have cited additional reference within the Supporting Information. [41] The Supporting Information contains a Materials and Methods description and additional UPLC chromatograms, LC-MS analysis, Transmission Electron Microscopy, confocal images and peptide library characterization using rheology and turbidity measurements.…”

Section: Supporting Informationmentioning

confidence: 99%

Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels

Pol,

Dai,

Thomann

et al. 2024

Angewandte Chemie

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

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“…These results indicate that condensates can both readily emerge from simpler building block components and play a role in shaping the distribution of polymer products. [81] Indeed, further studies utilized crossreactive dithiol peptide [82] building blocks and aminoacyl phosphate esters [83] that self-sort as self-replicating fibers and foldamers, illustrating how material properties can drive polymer selection (Figure 2).…”

Section: A Prebiotic Inventory Of Polymers Can Be Shaped By Compartmentsmentioning

confidence: 99%

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

Schnorr,

Childers

2024

ChemSystemsChem

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

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Spontaneous and Selective Peptide Elongation in Water Driven by Aminoacyl Phosphate Esters and Phase Changes

Cited by 17 publications

References 63 publications

Guiding Transient Peptide Assemblies with Structural Elements Around Abiotic Phosphate Fuels

Guiding Transient Peptide Assemblies with Structural Elements Around Abiotic Phosphate Fuels

Guiding Transient Peptide Assemblies with Structural Elements Embedded in Abiotic Phosphate Fuels

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

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