Abstract Structural adaption in living systems is achieved by competing catalytic pathways that drive assembly and disassembly of molecular components under the influence chemical fuels. We report on a simple mimic such system displays transient, sequence‐dependent formation supramolecular nanostructures based biocatalytic hydrolysis self‐assembling tripeptides. The are catalyzed α‐chymotrypsin driven dipeptide aspartyl‐phenylalanine‐methyl ester (the sweetener aspartame, DF‐OMe). observed...

We demonstrate the use of dipeptide amphiphiles that, by hand shaking a biphasic solvent system for few seconds, form emulsions that remain stable months through formation nanofibrous networks at organic/aqueous interface. Unlike absorption traditional surfactants, interfacial self-assembly π-stacking interactions and hydrogen bonding. Altering sequence has dramatic effect on properties formed, illustrating possibility tuning emulsion chemical design. The systems provide superior long-term...

Abstract The reversible regulation of catalytic activity is a feature found in natural enzymes which not commonly observed artificial systems. Here, we fabricate an hydrolase with pH‐switchable activity, achieved by introducing histidine residue at the terminus pH‐responsive peptide. peptide exhibits conformational transition from random coil to β‐sheet changing pH acidic alkaline. self‐assembles form long fibrils hydrophobic edge and residues extending ordered array as microenvironment,...

Folding can bestow macromolecules with various properties, as evident from nature's proteins. Until now complex folded molecules are the product either of evolution or an elaborate process design and synthesis. We show that fold in a well-defined architecture substantial complexity emerge autonomously selectively simple precursor. Specifically, we have identified self-synthesizing macrocyclic foldamer unprecedented secondary tertiary structure constructs itself highly 15 identical...

Abstract Among the key characteristics of living systems are their ability to self‐replicate and fact that they exist in an open system away from equilibrium. Herein, we show how outcome competition between two self‐replicators, differing size building block composition, is different depending on whether experiments conducted a closed vial or out‐of‐equilibrium replication–destruction regime. In system, slower replicator eventually prevails over faster competitor. replication‐destruction...

We demonstrate the self-assembly of bola-amphiphile-type conjugates dipeptides and perylene bisimide (PBI) in water other polar solvents. Depending on nature peptide used (glycine-tyrosine, GY, or glycine-aspartic acid, GD), balance between H-bonding aromatic stacking can be tailored. In aqueous buffer, PBI-[GY]2 forms chiral nanofibers, resulting formation a hydrogel, while for PBI-[GD]2 achiral spherical aggregates are formed, demonstrating that sequence has profound effect structure...

Abstract The properties of supramolecular materials are dictated by both kinetic and thermodynamic aspects, providing opportunities to dynamically regulate morphology function. Herein, we demonstrate time‐dependent regulation self‐assembly connected, kinetically competing enzymatic reactions. Starting from Fmoc‐tyrosine phosphate phenylalanine amide in the presence an amidase phosphatase, four distinct self‐assembling molecules may be formed which each give rise morphologies (spheres,...

We demonstrate an <italic>in situ</italic> ultrasonic approach to generate anisotropic organo- and hydrogels consisting of oriented tripeptides self-assembled structures.

The conditions that led to the formation of first organisms and ways life originates from a lifeless chemical soup are poorly understood. recent hypothesis "RNA-peptide coevolution" suggests current close relationship between amino acids nucleobases may well have extended origin life. We now show how interplay these compound classes can give rise new self-replicating molecules using dynamic combinatorial approach. report two strategies for fabrication chimeric acid/nucleobase macrocycles...

Nature chose phosphates to activate amino acids, where reactive intermediates and complex machinery drive the construction of polyamides. Outside biology, pathways mechanisms that allow spontaneous selective peptide elongation in aqueous abiotic systems remain unclear. Herein we work uncover those by following chemistry aminoacyl phosphate esters, synthetic counterparts adenylates. The esters act as solubility tags, making hydrophobic acids their oligomers soluble water enabling different...

Abstract Dynamic covalent chemistry (DCC) has proven to be a valuable tool in creating fascinating molecules, structures, and emergent properties fully synthetic systems. Here we report system that uses two dynamic bonds tandem, namely disulfides hydrazones, for the formation of hydrogels containing biologically relevant ligands. The reversibility disulfide allows fiber upon oxidation dithiol‐peptide building block, while reaction between NH−NH 2 functionalized C‐terminus aldehyde...

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....

Ultrasound, <italic>i.e.</italic> high frequency oscillating pressure waves, was used to achieve transient reorganization of supramolecular peptide nanostructures, which revert back the original state when sound is switched off.

Correlations between hydrogen bonds and solvent effects on phenol -OH proton shieldings, temperature coefficients (Δδ/ΔT) OH diffusion for numerous phenolic acids, flavonols, flavones, oleuropein derivatives of biological interest were investigated in several organic solvents shown to serve as reliable indicators bonding solvation state groups. The span a range -0.5 -12.3 ppb K(-1). Shielding differences 2.0 2.9 ppm at 298 K observed exposed groups DMSO-d(6) CD(3)CN which should be compared...

Gemcitabine, a drug with established efficacy against number of solid tumors, has therapeutic limitations due to its rapid metabolic inactivation. The aim this study was the development an innovative strategy produce metabolically stable analogue gemcitabine that could also be selectively delivered prostate cancer (CaP) cells based on cell surface expression Gonadotropin Releasing Hormone-Receptor (GnRH-R). synthesis and evaluation conjugated molecules, consisting linked GnRH agonist, is...

The ability to design reaction networks with high, but addressable complexity is a necessary prerequisite make advanced functional chemical systems. Dynamic combinatorial chemistry has proven be useful tool in achieving complexity, however some limitations controlling it. Herein we introduce the concept of antiparallel chemistries, which same group can channeled into one two reversible chemistries depending on controllable parameter. Such systems allow both for by chemistry, and addressing...

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...

Despite progress, a fundamental understanding of the relationships between molecular structure and self-assembly configuration Fmoc-dipeptides is still in its infancy. In this work, we provide combined experimental computational approach that makes use free energy equilibration number related to arrive at an atomistic model Fmoc-threonine-phenylalanine-amide (Fmoc-TF-NH2) which forms twisted fibres. By using dynamic peptide libraries where closely dipeptide sequences are dynamically...

The ability of molecules and systems to make copies themselves the fold into stable, well-defined three-dimensional conformations are considerable importance in formation persistence life. question how, during emergence life, oligomerization reactions become selective channel these toward a small number specific products remains largely unanswered. Herein, we demonstrate fully synthetic chemical system where structurally complex foldamers self-replicating assemblies emerge spontaneously with...

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....

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...

We show enzymatic introduction of non-natural amino acids with different electronic substituents a dramatic influence on morphology in self-assembled nanostructures.