Chiral molecules show left and right-handed nature in the sense that the molecules may exist as mirror-image forms that cannot be made to overlap by any amount of rotation.
The main cause of chirality in a molecule is that it has an atom often a carbon atom that is connected to four different groups in such a way that it is possible to have a non-superimposable image of the molecule. Such an atom is called a chiral center.
Although the carbon atom is the most common chiral center, Si, N, and P atoms are also known to act as chiral centers. The two mirror-image forms of a chiral compound are called enantiomers or optical isomers.
Molecules showing chirality have a special property: they rotate the plane of polarized light, and the degree of rotation is called specific rotation or optical rotation. For this reason, chiral centers are also called optical centers.
Racemic mixtures are those that have both enantiomers in equal proportion. They do not rotate polarized light, as the enantiomeric effects cancel each other out. When a molecule has more than one optical center, it may have 4 or 6 possible stereoisomers, not all of which may be enantiomers.
Such stereoisomers that are not enantiomers are called diastereomers. A majority of biomolecules amino acids, proteins, sugars, nucleic acids are chiral. And in nature, they exist in only one of two possible enantiomeric forms. In contrast, most monosaccharides exist only in dextrorotatory forms. Also, an amino acid such as threonine has two optical centers and four enantiomers, but of the latter, only one form is commonly found in nature.
All these indicate a preference for one form among all forms of a given molecule. The most obvious impact of chirality is seen in the shape of molecules.
The laevorotatory amino acids always give rise to right-handed helical proteins. Dextrorotatory amino acids, on the other hand, always give the right to left-handed proteins. A mixture of both forms cannot form helices at all. Similarly, the genetic material deoxyribonucleic acid is always coiled as a right-handed helix.
A more important consequence of chirality is that it influences the functional properties of biomolecules in a tremendous way. Simple sugar glucose is right-handed and is metabolized by the body.
Left-handed glucose, on the other hand, is not metabolized by the body. Chirality, an inherent property of peptides, has been recognized as a vital factor that can exert essential impacts on peptide assembly structures.
Since the thalidomide incident in the s, the importance of molecular chirality has been recognized. Therefore, in the development of peptide biomaterials, the chirality of peptides and amino acid residues is an important factor that has been taken into consideration by researchers. It has been suggested that amino acids and peptides with different chirality have different effects on protein adsorption Wang et al.
With the rapid development of supramolecular chemistry and the promising application of peptide assembly structures in the field of biomedicine, the influence of molecular chirality on the structure and function of peptide assemblies has been a key and hot research field.
In this mini review, we focus on the chirality effects in peptide assemblies. We summarized the recent advances in the structurally regulatory effects of chirality alteration on linear and cyclic peptide assemblies. Chiral self-sorting and co-assembly of mixed racemic peptides were discussed. Besides, we analyzed the influence of the chirality effects on the biological activities of peptide assembly structures.
Introducing D -amino acids into L -peptides can distort their main chains and destroy their original secondary structure. Chirality alteration of amino acid residues can break the secondary structure of peptides, thereby destroying their assembly structures. We studied the effects of chirality switching of a single amino acid residue at different positions and with various side chain moieties on peptide assembly structure using scanning tunneling microscope STM that is a very useful tool in studying peptide assembly structures at the single-molecule level Yu et al.
The above results indicate that heterochirality leads to weakening self-assembly propensity for some sequences. In contrast, for some sequences, they can still form ordered nanostructures after D -amino acid incorporation, just with the morphology and handedness of their assembly structures being changed. The effects of amino acid chirality alteration on the assembly structures of diphenylalanine FF and its derivatives have been investigated.
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.
As shown in Figure 1A , the dimension and pitch greatly exceeded those of the fibers formed by the homochiral analogs. The supramolecular chirality of peptide assemblies can be regulated by the chirality of single amino acid residue. It was shown that all the peptides self-assembled into twisted fibers, just with different twisted handedness which was found to be controlled by the chirality of the C-terminal hydrophilic Lys head Figure 1B Wang M.
The assembly structures of fatty chain-modified dialanine with homochirality and heterochirality have been characterized, showing that the handedness of the fibers was dependent on the chirality of the terminal alanine Fu et al. These results indicate the significance of the chirality of terminal amino acid residues in determining supramolecular chirality. On the contrary, Feng and coworkers studied the assembly structures of dipeptides derivatives by connecting two dipeptide arms FF, AA, FA, and AF with different chirality to para-disubstituted phenyl group, and found that the supramolecular chirality was only determined by the amino acid residue adjacent to the benzene core and irrespective of the chirality of C-terminal amino acid residue Qin et al.
In addition, the handedness of the nanofibers formed by bola-type dipeptides AF was dictated by the phenylalanine residue, not by the terminal amino acid residues Zheng et al. Figure 1. The effects of amino acid chirality alteration on peptide assembly structure.
Reproduced with permission from Clover et al. Copyright American Chemical Society. B The handedness of fibers formed by I 3 K is controlled by the chirality of the C-terminal hydrophilic Lys. Reproduced with permission from Wang M. Unexpectedly, some sequences showed a divergent trend that heterochirality made them prone to self-organization. Taking LFF as an example, the authors investigated the molecular mechanism by combining molecular modeling and X-ray diffraction XRD , and found that D LFF formed a phenylalanine zipper structure that promoted its self-assembling, and it was not accessible for the homochiral LFF due to steric hindrance from the side chain of the L -leucine Marchesan et al.
In , Marchesan et al. They speculated that this alternating arrangement of L - and D -amino acid could make all the hydrophobic amino acid side chains located on one side of the main chain of the peptide.
As a result, the side chains function as a hydrophobic part, and the main chains act as a hydrophilic part, which gives the heterochiral tripeptides amphiphilicity and facilitates their self-assembling and the formation of hydrogels.
The experimental results were consistent with the prediction showing that the heterochiral tripeptides self-assembled into fibrillar hydrogels, while most homochiral tripeptides formed amorphous aggregates. The overall configuration of peptide has a significant impact on its self-assembled structure.
L -peptide and D -peptide can form fibers with different handedness Koga et al. In general, L -peptide forms left-handed helical structure, while its enantiomer D -peptide forms right-handed helical structure. Nevertheless, there are many exceptions. Compared with linear peptides, literature reports on the chirality effects in assembly structures of cyclic peptides are far fewer.
There are a few reports on the chirality effects on cyclic dipeptides, the simplest cyclic peptide Govindaraju et al. As in linear peptides, chirality switching of amino acid residues can regulate morphology and macroscopic propensities of cyclic peptide assemblies. The 2D mesosheets formed by cyclo- Phg- D Phg are more thermodynamically stable than the mesosheets formed by cyclo- Phg-Phg Govindaraju et al.
For cyclic peptides with more than two amino acid residues that can self-organize into ordered structures, most of them are composed of alternating D - and L -amino acid residues. In , according to theoretical analysis, Santis et al.
Therefore, the self-assembled cyclic peptides almost take the arrangement of alternating D - and L -amino acid residues and exclusively self-assemble into nanotubes Insua and Montenegro, ; Song et al. In , Li et al. 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.
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.
In recent years, researchers have paid more and more attention to the assembly structures of racemic peptide mixtures. Chiral selectivity is ubiquitous in nature, so it is expected that proteins and peptides tend to prefer homochiral molecular interactions.
However, it has been demonstrated that mixing enantiomers can change the kinetics, morphology, and mechanical properties of peptide self-assemblies Nagy-Smith et al. For example, the racemic mixture of Fmoc monosubstituted cyclo- EE and its D -analog formed quickly recoverable thixotropic hydrogel with a significantly shortened thixotropic recovery time compared with the hydrogels formed by either enantiomer alone Wang L.
In addition, the racemic gel formed by diphenylalanine-based derivative enantiomers was more mechanically robust than the gels formed by either pure enantiomer Qin et al. On the contrary, He and coworkers got the opposite results showing that the hydrogel formed by a racemic mixture of ferrocene-diphenylalanine Fc-FF was mechanically weaker than the enantiopure hydrogels Zhang et al.
These differences in assembly behaviors between racemic mixtures and the pure enantiomers suggest that racemic mixtures may form a distinct new structure.
Amyloid peptide polyglutamine polyQ was found to lack stereochemical restriction in seeded elongation of its amyloid fibers, as the fibrils formed by D-polyQ could efficiently seed the aggregation of L-polyQ monomers in vitro , and vice versa Kar et al.
Besides, enantiomeric amino acids can co-assemble into nanostructures with enhanced mechanical rigidity. The Gazit group explored the assembly behaviors of the mixed aromatic amino acid enantiomers Phe and Trp via diverse experimental techniques Bera et al. It was revealed that enantiomeric amino acids co-assembled into nanostructures with different morphology and kinetics compared with the pure enantiomers.
As shown in Figure 2B , the pure enantiomers formed unbranched fibers, while the mixed enantiomers co-assembled into crystalline flake-like structure that was mechanically more robust than the enantiopure fibers.
For example, the Nanda group found that mixing a collagen mimetic peptide PPG 10 and its D-analog DPDPG 10 drastically lowered the solubility, as they assembled into sheets and precipitated from the buffer solution, while in the same condition, individual enantiomer was soluble Xu et al.
Combining the results of experiments and computational simulation, the authors postulated that this helix peptide favored heterochiral association, since left- and right-handed molecular screws could interdigitate and pack more tightly Figure 2C.
Figure 2. Co-assembly structures of racemic peptides and amino acids. Reproduced with permission from Nagy-Smith et al. B The co-assembly structure of L -Phe and D -Phe is totally different from the self-assembly structure of the pure enantiomers.
Reproduced with permission from Bera et al. Reproduced with permission from Xu et al. Introducing D -amino acids into self-assembled L -peptides is widely used to improve the enzymatic stability of their assembly structures, while it can also affect their biological functions. It was revealed that F D F could also self-assemble into nanotubes like its L -enantiomer, but the heterochirality completely alleviated its amyloid cytotoxicity Kralj et al.
Fibers formed by fatty chain-modified L -V 3 A 3 K 3 showed higher cytotoxicity than the fibers formed by its D -analog, which was ascribed to the stronger affinity between the L -peptide and lipid Sato et al. The macromolecules involved in protein biosynthesis such as aminoacyl tRNA synthetase and ribosome have chiral subunits. Despite the omnipresence of chirality in the biosynthetic pathway, its origin, role in current pathway, and importance is far from understood.
In this review we first present an introduction to biochirality and its relevance to protein biosynthesis. Major propositions about the prebiotic origin of biomolecules are presented with particular reference to proteins and nucleic acids.
The problem of the origin of homochirality is unresolved at present.
0コメント