Noncovalently Bridging Cell-Surface Proteins Using Synthetic Peptides to Modulate Cell Apoptosis.

Controlled high-order clustering of cell-surface proteins is an essential but unmatched regulatory mechanism in living systems for the modulation of cell behavior. Here, we present a strategy for generating extended and tunable one-dimensional clusters of death receptors on live cell surfaces by employing synthetic peptides to noncovalently bridging the proteins. The on-cell assembly process is validated through super-resolution fluorescence imaging and fluorescence lifetime imaging analyses.

Peptide Designs for Cell-Interfacing Assemblies.

Constructing synthetic materials to interact with cells offers significant promise for understanding natural cellular processes and manipulating cell behaviors beyond nature's capabilities. Peptide assemblies are particular promising in this regard, as they have demonstrated efficacy in promoting cell differentiation, repair, and regeneration as supportive scaffolds. However, distinct gaps persist between natural and synthetic assembly systems in various aspects.

Self-Assembled Peptide Sheet-Mediated Multivalent Capture of Cells with Enhanced Tunability.

We report the creation of multivalent ligand surfaces for cell capture by conjugation of ligand-appended 2D peptide assemblies on an antifouling glass substrate. The sheet-like structures organize ligands into non-uniform, patchy patterns, enhancing multivalent cell targeting. A 155 % increase in captured cells was achieved compared to the presentation of the ligands on surfaces lacking the peptide sheets.

Self-Assembled Bent Perylenediimides.

The properties of π-functional materials are predominantly influenced by both their molecular structures and interactions between π-systems. Recent advancements have focused on modifying the geometry or topology of π-molecules from planar to nonplanar conformations to tailor molecular properties. However, the interactions among nonplanar π-molecules remain largely unexplored, likely due to the significant reduction in contact surfaces arising from their curved structures.

Heterochiral coupling to bilateral β-turn structured azapeptides bearing two remote chiral centers.

Enantioselective synthesis governed by chiral catalysts has been extensively developed, but that without any chiral auxiliaries or chiral catalysts is rare, particularly when remote stereogenic centers are involved. Here we report an enantioselectivity of heterochiral coupling in the one-pot reaction of racemic hydrazides with achiral 1,4-bis(isothiocyanine)benzene, yielding preferentially the heterochiral bilateral azapeptides over the homochiral ones. Despite bearing two hydrogen-bonded β-turn structures that allow intramolecular chiral transfer, the bilateral azapeptide products have two chiral centers separated by 14 atoms or 15 bonds, which prevent the direct intramolecular asymmetric communication between the two chiral centers.

Simultaneous formation of helical and sheet-like assemblies from short azapeptides enables spontaneous resolution.

As determined by the homochirality of amino acid building units, protein secondary structures α-helix and β-sheet are single-handed chiral superstructures extending in one and quasi-two dimensions, respectively. Synthetic molecular assemblies that mimic the structural homochirality of proteins would provide insights into the origin of biological homochirality and inform the development of chiral separation techniques. Here we fabricated a homochiral 3D assembly consisting of 1D helical and 2D sheet-like assemblies that feature molecular packings resembling α-helix and β-sheet, respectively.

Supramolecular helix of an oligomeric azapeptide building block containing four β-turn structures.

Oligomers of benzoylalanine-based amidothioureas containing four β-turn structures spaced by -substituted benzenes were shown to undergo assembly in dilute CHCN solution into supramolecular helices of enhanced supramolecular helicity, whereas those spaced by -substituted benzene spacer(s) or those spaced by -substituted benzenes but with one or two β-turns exhibit a substantially decreased tendency of assembling.

Preserving Structurally Labile Peptide Nanosheets After Molecular Functionalization of the Self-Assembling Peptides.

A significant challenge in creating supramolecular materials is that conjugating molecular functionalities to building blocks often results in dissociation or undesired morphological transformation of their assemblies. Here we present a facile strategy to preserve structurally labile peptide assemblies after molecular modification of the self-assembling peptides. Sheet-forming peptides are designed to afford a staggered alignment with the segments bearing chemical modification sites protruding from the sheet surfaces.

Amyloid peptide hydrogels formation of coordination polymers with Ag by its core peptide equipped with a C-cysteine.

We report that the core sequence of amyloid β (Aβ) peptide, KLVFF, when equipped with a C-terminal cysteine residue, exhibited an extremely low minimum hydrogelation concentration of 0.05 wt% in the presence of Ag in pH 5 buffer, with this concentration 2 orders of magnitude lower than that of the pentapeptide itself. The CD signal of the Ag-L-KLVFFC hydrogel was observed to be sensitive to the early-stage aggregation of amyloid β peptide.

Reassembly of Peptide Nanofibrils on Live Cell Surfaces Promotes Cell-Cell Interactions.

Nature regulates cellular interactions through the cell-surface molecules and plasma membranes. Despite advances in cell-surface engineering with diverse ligands and reactive groups, modulating cell-cell interactions through scaffolds of the cell-binding cues remains a challenging endeavor. Here, we assembled peptide nanofibrils on live cell surfaces to present the ligands that bind to the target cells.

One-Pot Cyclization to Large Peptidomimetic Macrocycles by In Situ-Generated β-Turn-Enforced Folding.

Macrocycles have been targets of extensive synthetic efforts for decades because of their potent molecular recognition and self-assembly capabilities. Yet, efficient syntheses of macrocyclic molecules via irreversible covalent bonds remain challenging. Here, we report an efficient approach to large peptidomimetic macrocycles by using the in situ-generated β-turn structural motifs afforded in the amidothiourea moieties from the early steps of the reaction of 2 molecules of bilateral amino acid-based acylhydrazine with 2 molecules of diisothiocyanate.

Design of Multicomponent Peptide Fibrils with Ordered and Programmable Compositional Patterns.

Advanced applications of biomacromolecular assemblies require a stringent degree of control over molecular arrangement, which is a challenge to current synthetic methods. Here we used a neighbor-controlled patterning strategy to build multicomponent peptide fibrils with an unprecedented capacity to manipulate local composition and peptide positions. Eight peptides were designed to have regulable nearest neighbors upon co-assembly, which, by simulation, afforded 412 different patterns within fibrils, with varied compositions and/or peptide positions.

Aggregated coordination polymers of Ag with a cysteine derivative ligand containing an AIEgen.

We investigated coordination polymers of Ag with a cysteine-based thiol ligand designed to contain a tetraphenylethylene AIEgen (L- and D-1). The coordination polymers, forming in a variety of protic and aprotic organic solvents, such as THF, CHCN and CHOH, were shown to undergo aggregation in HO/THF binary solvents at water volume fractions above 50%, where emission was substantially enhanced while the CD profile was reversed, yet the dependence of the CD signal on ee remained S-shaped for the polymers in the aprotic organic solvents THF and CHCN, in contrast to that in protic solvents CHOH and CHOH.

Unequal Perylene Diimide Twins in a Quadruple Assembly.

Natural light-harvesting (LH) systems can divide identical dyes into unequal aggregate states, thereby achieving intelligent "allocation of labor". From a synthetic point of view, the construction of such kinds of unequal and integrated systems without the help of proteinaceous scaffolding is challenging. Here, we show that four octatetrayne-bridged ortho-perylene diimide (PDI) dyads (POPs) self-assemble into a quadruple assembly (POP) both in solution and in the solid state.

Synthetic approaches to metal-coordination-directed macrocyclic complexes.

Metal-coordination-directed macrocyclic complexes, in which macrocyclic architectures are formed by metal-ligand coordination interactions, have emerged as attractive supramolecular scaffolds for the creation of materials for applications in biosensing and therapeutics. Despite recent progress, uncontrolled multicyclic cages and linear oligomers/polymers is the most likely outcome from metal-ligands assembly, representing a challenge to current synthetic methods. Herein we outlined the state-of-art synthetic approaches to the metal-coordination-directed macrocyclic complexes by using foldable ligands or through assembly of amphiphilic ligands.

Design of high-avidity multivalent ligand structures that target cells with high ligand economy.

Novel cell-targeting ligand structures are constructed with a spikey core scaffold, where multiple copies of coiled-coil peptide nanorods are conjugated on the surface of a peptide nanosheet. Clustering of carbohydrate and aptamer ligands at the end of the coiled coils optimizes ligand accessibility to cell-surface receptors. Display of the ligand-coil conjugates on the nanosheet generates a patchy ligand pattern bearing two levels of multivalency.

Measuring anion binding at biomembrane interfaces.

The quantification of anion binding by molecular receptors within lipid bilayers remains challenging. Here we measure anion binding in lipid bilayers by creating a fluorescent macrocycle featuring a strong sulfate affinity. We find the determinants of anion binding in lipid bilayers to be different from those expected that govern anion binding in solution.

Spontaneous Resolution of Helical Building Blocks through the Formation of Homochiral Helices in Two Dimensions.

Spontaneous resolution leading to conglomerate crystals remains a significant challenge. Here we propose the formation of orthogonal homochiral supramolecular helices in at least two dimensions to allow spontaneous resolution. We suggest the design rationale that the chiral species is made into helical building blocks to allow the helix formation.

Intramolecular chalcogen bonding to tune the molecular conformation of helical building blocks for a supramolecular helix.

We propose to employ intramolecular chalcogen bonding to make a helical building block take its otherwise unfavorable -conformation. The 2,5-thiophenediamide motif was taken to bridge two β-turn structures to lead to an azapeptide that exists in -conformation and forms a halogen-bonded single-strand helix that exhibits a much stronger supramolecular helicity and a higher thermal stability.

- and -Shaped Perylene Diimide Heterohelicenes: Modular Synthesis and Spiral-Stair-Like π-Stacking.

A number of - and -shaped perylene diimide (PDI) heterohelicenes with high dipole moments were synthesized from simple perylene tetrabutylester (PTE). Taking advantage of the weak coordination ability of the sterically crowded peri ester groups in PTE, efficient Rh(III)-catalyzed 2,8- and 2,11-bisiodinations of the perylene core were realized. The 2,8- and 2,11-diiodinated PTEs and PDIs represent key synthons for further -π-extensions.

Supramolecular helices from helical building blocks head-to-tail intermolecular interactions.

Supramolecular helices from helical building blocks represent an emerging analogue of the α-helix. In cases where the helicity of the helical building block is well propagated, the head-to-tail intermolecular interactions that lead to the helix could be enhanced to promote the formation and the stability of the supramolecular helix, wherein homochiral elongation dominates and functional helical channel structures could also be generated. This feature article outlines the supramolecular helices built from helical building blocks, , helical aromatic foldamers and helical short peptides that are held together by intermolecular π-π stacking, hydrogen/halogen/chalcogen bonding, metal coordination, dynamic covalent bonding and solvophobic interactions, with emphasis on the influence of efficient propagation of helicity during assembly, favouring homochirality and channel functions.

Chalcogen bonding mediates the formation of supramolecular helices of azapeptides in crystals.

To explore whether chalcogen bonding was able to drive the formation of supramolecular helices, alanine-based azapeptides containing a β-turn structure, with a thiophene group, respectively, incorporated in the N- or C-terminus, were employed as helical building blocks. While the former derivative formed a supramolecular M-helix via intermolecular SS chalcogen bonding in crystals, the latter formed P-helix via intermolecular SO chalcogen bonding.