Homochirality peptide

Chiral surfaces Enantiomorphous crystals Homochiral peptides Mirror symmetry breaking Non-linear kinetics Self-replication of peptides... 

Enantiomeric enrichment of homochiral peptides was achieved during partial hydrolysis of polypeptides composed from polymers that contain blocks of both random and a-helix [177] or random and /1-sheet sequences [178]. Hydrolysis of the atactic part of the polypeptides was found to occur much faster than within the isotactic blocks of a-helix and /3-sheets. Based on these observations, Bonner suggested that environmental dry/wet cycles on the primitive Earth might have caused repeated polymerization/hydrolysis cycles that permitted the eventual evolution of optical purity from a small abiotic ee value for the amino acids [177,179]. 

Fig. 22 A schematic representation of chiroselective replication cycles. Homochiral peptides Tll and Tdd are produced autocatalytically while the heterochiral peptides TDL and Tdl result from uncatalyzed background reactions. Template-directed ligation reactions proceed through the intermediary of stereospecific noncovalent complexes and pass on stereochemical information from the homochiral products to the substrates, thus resulting in the amplification of homochiral products. Light and dark backgrounds denote regions of the sequence composed of L- and D-amino acids, respectively (Reproduced from [218], Copyright 2001, Nature)...

Figure 6. Schematic representation of chiroselective self-replication of the homochiral peptide LL. Adapted with permission from reference 53. Copyright 2001 Nature Publishing Group.

Moreover, it was also resistant towards small errors in the template chain substitution of one monomeric unit by its enantiomer created a heterochiral template that nevertheless catalysed the formation of the homochiral peptide. The peptide s homochirality would be preserved this way even if racemization of some of its building blocks occiured. 

Fig. 2.35 y-Peptides studied by NMR and shown to adopt a 2.6,4-helical secondary structure. These include y-peptides with homochiral sequences consisting of enantio-pure y" -amino acid residues (139-142), y -amino acid residues of relative configuration... 

Another example of the ability of proteinogenic amino acids, small peptides, and amines to catalyse the formation of new C-C bonds has been demonstrated by Weber and Pizzarello they were able to carry out model reactions for the stereospecific synthesis of sugars (tetroses) using homochiral L-dipeptides. The authors achieved a D-enantiomeric excess (ee) of more than 80% using L-Val-L-Val as the peptide catalyst in sugar synthesis (in particular D-erythrose) via self-condensation of glycol aldehyde. 

In accordance with the autocatalytic process, matrices are again formed. It is surprising that the autocatalysis decreases when only 1 of the 15 building blocks of the peptide has the opposite handedness, e.g., when the N-peptide fragment contains one D-amino acid as well as the 14 L-amino acids. These experimental results show that such a system is able to form homochiral products via self-replication. It can be assumed that similar mechanisms influenced the origin of homochirality on Earth (Saghatelian et al., 2001 Siegel, 2001). 

The relevant AGB values, calculated by using Te = 970 are listed in Table 8. According to the reported values, the heterochiral Trp/Pro and Phe/Ala complexes are more stable than the homochiral ones. The reverse is true for the Phe/ Pro and PheA al complexes. By the same token, the chiral discrimination factor, AR measured by ESl-MS for 19 amino acids was found to vary between 0.3 and 3. ° The stereochemistry associated to the CID of diastereomeric peptides has been investigated using a similar approach. The results suggest that the secondary structure of protonated peptides may play an important role in their gas-phase behavior. ... 

Synthetic pathways towards the dimethylene isosteres comprise several disconnections, indicated by the essential bond forming reactions (Scheme 2). Several methods yield racemic dipeptide analogues. These are usually incorporated into the peptide sequence and the resulting epimeric peptides are separated. When either R1 or R2 = H, asymmetric syntheses towards the required enantiomer are available. When both R1 and R2 H, only the reduction of the i )[CH=CH] precursor yields homochiral compounds. As many co-amino acids (R1 = R2 = H) are commercially available, their synthesis needs not be discussed here. 

The presence of the additional p-carbon atom in Tau analogues offers the opportunity to study the influence of functionalization at this p-position as compared to functionalization at the a-position. Naturally occurring a-amino acids can be used as starting materials for the synthesis of homochiral P-substituted methylene sulfinamide and sulfonamide transition-state isosteres incorporated in peptides.11201... 

RNA but of both handednesses. Upon appending a single homochiral residue such as L-lysine at the carboxy terminus of the helix, the peptide nucleic acid polymers predominantly fold into duplexes of a single handedness. This phenomenal positive cooperativity can be considered a form of molecular amplification. Additional examples on spontaneous and induced formations of helical morphologies were reviewed [114,182]. 

The formation of racemic mixtures of homochiral oligopeptides is not confined to racemates undergoing spontaneous segregation into enantiomor-phous domains it can also be extended to racemic 2-D crystallites, provided the reaction pathway takes place preferentially between homochiral molecules related by translation symmetry, as in the case of the thioethylester of N -slearoyl-lysinc (Cis-TE-Lys) [193]. It has been experimentally proven by GIXD that racemic Cis-TE-Lys self-assemble into racemic 2-D crystallites, Fig. 15. Moreover, MALDI-TOF MS analyses of oligopeptide samples obtained from the polycondensation of deuterium enantiolabeled monomers have revealed a clear trend toward enhanced formation of di- to hexa-peptides with homochiral sequences, in agreement with a reaction pathway between homochiral monomer molecules related by translation symmetry [193,195]. 

Fig.20 MALDI-TOF mass spectrum of the oligopeptides obtained in the polymerization of (DL)-PheNCA at 22 °C, showing the m/z range from penta- to decapeptides. The two insets show expanded spectra of the octa- and nonapeptide ranges. The peaks at the wings of each group showing peptides of the same length represent molecules of homochiral sequence...

It has been discovered that homochrral amino acids undergo slow racemization under the conditions of the peptide cycle, which may be attributed to the hydantoin stage. Racemic amino acids are actually an advantage from the point of view of ligand feedback, because racemic amino acids generate a greater variety of peptides than homochiral amino acids. 

In the course of evolution of the metabolism by peptide feedback, the system will sooner or later become homochiral because of symmetry breaking by autocatalytic feedback. At this level it has been shown that a-amino acids undergo a facile enantioselective conversion to thermostable fS-sheets (19). 

Solids that strongly attract water and other polar solvents are the common media for achieving classical column-chromatographic separation of amino acids and peptides, on the basis of the partition principle (Hearn, 1991 Hancock, 1984). Cellulose (i.e. paper in the form of sheets or powder), one of the media of this type used since the earliest days of chromatography, also has the capacity to bind, through adsorbed water, to one enantiomer of certain amino acids, e.g. tryptophan, more strongly than to the opposite enantiomer (chiral or enantioselective separation chromatographic resolution), because cellulose is homochiral (constructed purely of one enantiomer). 

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