Self-Assembly of Block Heterochiral Peptides into Helical Tapes

Abstract

Patterned substitution of d -amino acids into the primary sequences of self-assembling peptides influences molecular-level packing and supramolecular morphology. We report that block heterochiral analogs of the model amphipathic peptide KFE8 (Ac-FKFEFKFE-NH 2 ), composed of two FKFE repeat motifs with opposite chirality, assemble into helical tapes with dimensions greatly exceeding those of their fibrillar homochiral counterparts. At sufficient concentrations, these tapes form hydrogels with reduced storage moduli but retain the shear-thinning behavior and consistent mechanical recovery of the homochiral analogs. Varying the identity of charged residues (FRFEFRFE and FRFDFRFD) produced similarly sized nonhelical tapes, while a peptide with nonenantiomeric l - and d -blocks (FKFEFRFD) formed helical tapes closely resembling those of the heterochiral KFE8 analogs. A proposed energy-minimized model suggests that a kink at the interface between l - and d -blocks leads to the assembly of flat monolayers with nonidentical surfaces that display alternating stacks of hydrophobic and charged groups.

Chirality Effects in Peptide Assembly Structures

“…In terms of structure, most studies focus on the effects of chirality alteration on the morphology, size, and secondary structure of peptide assemblies, while the molecular mechanisms for these effects are relatively less explored. It is worth noting that many researchers have combined Molecular Dynamics (MD) calculations with experimental data and successfully elucidated the molecular basis for the changes in the assembly structures of peptides caused by chirality conversion ( Wang M. et al, 2017 ; Clover et al, 2020 ). Therefore, the combination of computational approaches and an arsenal of experimental techniques is supposed to be a useful tool to undercover the chirality effects in peptide assemblies on the molecular level.…”

“…It was suggested that replacing one Phe of FF with its D -enantiomer preserved its ability to self-assemble into nanotubes and the heterochirality made the nanotubes more homogeneous and stable ( Kralj et al, 2020 ), while switching the chirality of one Phe of FF derivatives, such as Fmoc-FF-Fmoc and Nap-FF, changed the morphology of their assembly structures ( McAulay et al, 2019 ; Gil et al, 2020 ). The Rudra group explored the effects of multiple and consecutive amino acid chiral mutations on the assembly structure of peptide Ac-(FKFE) 2 -NH 2 ( Clover et al, 2020 ). The results showed that the heterochiral analogs of the model peptide, composed of two FKFE repeat motifs with opposite chirality, self-assembled into helical tapes with a width of 108 ± 55 nm and a pitch of 900–1200 nm.…”

“…(A) Amino acid chirality alteration drastically changes the morphology of assembly structure of the peptide Ac-(FKFE) 2 -NH 2 . Reproduced with permission from Clover et al (2020) . Copyright 2020 American Chemical Society.…”

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

“… 33 Heterochirality is gaining momentum as a strategy to tailor peptide self-assembly. 34 − 36 Uncapped dipeptides are very attractive building blocks due to their chemical simplicity. Furthermore, enantiomers are expected to display the same self-assembly behavior in achiral environments, therefore, investigation of compounds 2 – 6 will shed light also on the self-assembly of their mirror-image l - d dipeptide isomers.…”

Two‐dimensional metal organic frameworks for biomedical applications

“…Highly ordered and solid‐state porous two‐dimensional (2D) nanomaterials are a new class of materials (Karak et al, 2017; Karak, Kumar, Pachfule, & Banerjee, 2018; Zhang et al, 2019), that have shown wide‐spread applications in catalysis (Chen, Zhang, Jiao, & Jiang, 2018), sensing (Das et al, 2015; Ding et al, 2016; Ma et al, 2018), biomedical (Fang, Kim, Kim, & Yu, 2013; Yang, Léonard, Lemaire, Tian, & Su, 2011), gas adsorption (Ma et al, 2018; Zhu et al, 2017), and energy storage (Kou et al, 2017). These 2D nanomaterials include graphitic carbon nitride (g‐C 3 N 4 ) (Wang, Zhang, Li, Li, & Wu, 2017; Zhang et al, 2013), transition metal dichalcogenides (TMDs; Carrow et al, 2020; Jaiswal, Singh, Lokhande, & Gaharwar, 2019; Lu, Yu, Ma, Chen, & Zhang, 2016; Zhang, Lai, Ma, & Zhang, 2018), covalent organic frameworks (COFs; Bhunia, Deo, & Gaharwar, 2020), hexagonal boron nitride (h‐BN; Deshmukh, Jeong, Lee, Park, & Kim, 2019; He et al, 2019), layered double hydroxides (LDHs; Yu, Wang, O'Hare, & Sun, 2017; Zhao et al, 2017), layered silicates (nanoclay) (Gaharwar et al, 2019), polymer sheets (Clover et al, 2020), and noble metal nanosheets (Huang et al, 2011; Sancho‐Albero et al, 2019). Diverse biomedical applications of these nanomaterials are owing to their versatile properties including high surface area, high conductivity, and superior optical properties (Brokesh & Gaharwar, 2020; Chimene, Alge, & Gaharwar, 2015; Gaharwar, Singh, & Khademhosseini, 2020; Lee & Gaharwar, 2020).…”