Modulating the Nucleated Self‐Assembly of Tri‐β³‐Peptides Using Cucurbit[n]urils

Abstract

The modulation of the hierarchical nucleated self-assembly of tri-b 3 -peptidesh as been studied. b 3 -Tyrosine provided ah andle to control the assembly process throughh ost-guest interactions with CB [7] and CB [8]. By varyingt he cavity size from CB [7] to CB [8] distinct phases of assembling tri-b 3 -peptides were arrested. Given the limited size of the CB [7] cavity,o nly one aromatic b 3 -tyrosine can be simultaneously hosted and, hence,C B [7] was primarily acting as an inhibitor of self-assembly.I ns trong contrast, the larger CB [8] can form at ernary complex with two aromatic amino acids and hence CB[8] wasa cting primarily as cross-linker of multiple fibersa nd promoting the formation of larger aggregates. General insights on modulating supramolecular assembly can lead to new ways to introduce functionality in supramolecular polymers.Our understanding of how synthetic peptides and other molecular systems self-assemble into helical structures has progressedi nr ecent decades towards ap rocesst hat mimics many aspects of nucleated assembly of proteins observed in nature. [1][2][3][4][5][6] As expected, the nucleated assembly of peptides requires distinct sequence motifsa nd their assembly can be modulated using conventional factors such as concentration, pH, time, and temperature. More interestingly,t he onset and regulation of peptideassembly can be activated by light or enzymatics witches. [7,8] In spite of these advances, the programmabilityo ft he hierarchical assembly of synthetic peptides and molecules into highero rderedf ibrillar structures remains challenging in contrast to for example, naturallyo ccurring b-sheets that hierarchically assemble into dimers, tetramers, protofibrils, and finally large fibrillar aggregates. [9] In particular, recent researchh as demonstrated that the addition of chirala uxiliaries or seed molecules can lead to either the exclusive formationo f metastable helical aggregates or allows control over fibrillar width and length, as shown in mechanistic assembly studies on aromatic disc-and rod-likem olecules. [10][11][12][13][14] Promisingresults have also been reported by Moore and co-workerst oc ontrol the final outcome of the nucleated assemblyo fa-peptides by the addition of polymer-peptide conjugates into discrete nanostructures. [15] Very recently,t he addition of macrocycles CB [7] and CB[8] assisted the assembly of functional dimeric and tetramericp roteins, protein wires, and cell clusters mediated by interactions of these macrocyclesw ith aromatic amino acids in proteins. [16][17][18][19][20][21] SpecificC B[7]-phenyla laninei nteractions were used by Kim and co-workerst oi nhibit a-peptide fibril formation [22] and by Urbacha nd co-workers to inhibit an onspecific protease. [18] a-Peptides composed of lesst han 15 amino acids generally do not adopt defined helicalc onformations,i na bsence of structuralc onstraints.I ns trong contrast, as urprising aspecto f b-peptides is that they adopt defined helical structures over very short sequences despitet h...

Host–Guest Induced Peptide Folding with Sequence-Specific Structural Chirality

“…Control over the spatial and temporal behavior of peptide segments is of great importance for precisely engineering hierarchical protein structures, , inhibiting peptide and protein aggregation, , and developing stimuli-responsive materials. − Peptide architectures can be altered significantly by covalent modifications or through noncovalent molecular recognition. , These approaches typically require precise sequence design, along with the inclusion of unnatural amino acids to achieve the desired structural function. − …”