Macrochirality of Self-Assembled and Co-assembled Supramolecular Structures of a Pair of Enantiomeric Peptides

Abstract

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures.

An Exploration of Multiple Component Peptide Assemblies by Enzyme‐Instructed Self‐Assembly

“…Although the crystal structure of Merlin is predominantly a beta‐sheet protein and the anionic sequence of DCAF‐1 a beta strand, the common feature of CD signals in Figure 5 is the lack of strong beta sheet signal. The dominant band observed around 234 nm is likely associated with the CD signal of the amide bond that connects the Nap motif to diphenylalanine because its handedness switches with the change of the chirality of diphenylalanine [65] . As shown in Figure 5A, the CD signals of the solution of 1P or the hydrogel of 1 (at 250 μM) are the highest.…”

“…The dominant band observed around 234 nm is likely associated with the CD signal of the amide bond that connects the Nap motif to diphenylalanine because its handedness switches with the change of the chirality of diphenylalanine. [65] As shown in Figure 5A, the CD signals of the solution of 1P or the hydrogel of 1 (at 250 μM) are the highest. The addition of equal equivalent of 4 to 1P decreases the CD signals of the solutions and the hydrogels by 57 % and 53 %, respectively (Figure 5A).…”

Arrow of Time, Entropy, and Protein Folding: Holistic View on Biochirality

“…Although new achievements are commonly recognized, the adequate understanding of the link of chirality and entropy phenomena in biology, which embrace very remote areas, such as the electron nuclear spins coupling, protein folding, metabolism, memory, cognition and consciousness, are just in an embryonic state [ 116 , 117 , 118 , 119 , 120 , 121 ].…”

Biostable hydrogels consisting of hybrid β-sheet fibrils assembled by a pair of enantiomeric peptides

“…The inherent chirality of the peptides and proteins not only offers insights into fundamental biological processes but also presents opportunities for advancing supramolecular biomaterials. These materials are characterized by different fibril handedness [ 8 ], proteolytic susceptibility [ 9 ], and bioactivity [ 10 ], providing a versatile platform for various applications in chiral recognition [ 11 , 12 ], catalysis [ 13 ], cancer therapeutics [ 14 ], antimicrobial activity [ [15] , [16] , [17] ], and 3D cell culture [ 18 , 19 ].…”