Self-Assembly of Constrained Cyclic Peptides Controlled by Ring Size

Abstract

The de novo design of new peptide assemblies that expands the repertoire of biomaterial nanostructures has been of a tremendous challenge. Hence, it is evident that a successful research achievement in this area would increase the understanding of molecular interactions in supramolecules and create novel scaffolds exploitable in biotechnology and synthetic biology. The manipulation of cyclic peptide self-assembly is particularly intriguing for this purpose. Herein, we report that a novel type of cyclic peptides, referred to as chiral tether constrained cyclic peptides (CCP), shows promising self-assembly properties. CCPs are the first example of a controllable assembly of all-L-α-cyclic peptides with different ring sizes. A noteworthy feature of the CCP system is good tolerance of different secondary structures, ring size, and peptide sequence. Based on this system, a variety of nanostructures could be constructed, which display different physical properties, rendering it an excellent platform for molecular interaction studies. Further, demonstrate potential applications of these peptide assemblies in bioimaging and energy storage.

Chirality Effects in Peptide Assembly Structures

“…In 2018, Li et al introduced an in-tether chiral group to liner peptides and designed a type of cyclized helical peptides that only consist of L-amino acid residues. It has been revealed that this kind of peptide can self-assemble into well-ordered nanostructures, and their assembly behaviors can be governed by the in-tether chiral center (Hu et al, 2018(Hu et al, , 2020. For unmodified L-cyclic peptides, more explorations are needed to clarify their assembly propensity and the effects of chirality alteration on their assembly structures, which can not only broaden the building blocks of peptide assemblies, but also contribute to understanding the chirality effects in assembly structures of peptides with limited rotation and structural rigidity.…”

Mitochondria-Targeted Self-Assembly of Peptide-Based Nanomaterials

“…Particularly, self-assembling peptides have attracted increasing interest due to their improved stability and biological performance (Guyon et al, 2018;Levin et al, 2020), and have been applied in a wide range of fields including the tissue engineering (Gelain et al, 2020;Zhang et al, 2021), drug delivery (Moitra et al, 2014;Abbas et al, 2017;Yang J. et al, 2020;Kumar et al, 2020;, catalysis (Rufo et al, 2014;Wang M. et al, 2020;Liu Q. et al, 2021;Chen et al, 2021), semi-conducting device (Tao et al, 2017), and energy materials (Hu et al, 2018;Lee et al, 2018;Nguyen et al, 2021). With the molecular basis to form secondary structures including the α-helix and β-sheet, the self-assembling peptides can assemble into well-defined nanostructures like nanofibrils driven by non-covalent interactions, such as the hydrophobic interaction, electrostatic interaction, π-π stacking, hydrogen bond, etc (Hendricks et al, 2017;Hu et al, 2020;Zheng et al, 2021). For instance, the diphenylalanine peptide (FF), the most widely investigated selfassembling peptide, can assemble into either the nanofiber, nanotube, nanosphere, or nanoarray on the surface, by using properly mixed solvents and kinetic controls, or vapor deposition (Reches and Gazit, 2003;Wei et al, 2017;Zhao et al, 2019).…”

Self-Assembly of Constrained Cyclic Peptides Controlled by Ring Size

“…The 2-S and 3-S peptides mostly adopted random coil conformations, which are unfavorable for assembly. 34 The other CCP peptides were in either helical or antiparallel conformations, which are typical conformations adopted in peptide assemblies.…”

“…Currently, most investigative efforts are relying on exploiting the assembling of cyclic peptides that adopt βsheet or α-helix conformation. 29,49 However, the majority of those systems are sequence size-or ring-size-dependent and represent a limited potential for constructing various nanostructures. In this study, we have further explored our previously published CIA system by studying the relationship between ring size and self-assembly behavior.…”

“…Self-assembly, by nature, is ubiquitous and considered a bottom-up strategy for fabricating nanomaterials. 1,2 Peptide molecules are excellent building blocks for tunable, hierarchical self-assembly due to their numerous possible sequences, diverse conformations, and rich chemical functionalities. 3,4 Commonly used building blocks for peptide self-assembly include dipeptide of phenylalanine (FF) or their derivatives, 4,5 D,L-cyclic peptides, 6 peptide amphiphiles, 7 collagens, 8 coiled coils, 9 and foldectures.…”