Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Abstract

Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthday Racemic S-ethyl thioesters of N e -stearoyllysine ( S-ethyl (R,S)-2-amino-6-(stearoylamino)hexanethioate) and S-ethyl thioesters of g-stearyl glutamic acid ( stearyl (R,S)-4-amino-5-(ethylsulfanyl)-5-oxopentanoate) self-assemble as separated two-dimensional crystalline monolayers within an achiral phospholipid environment of racemic 1,2-dipalmitoylglycerol (DPG) and 1,2-dipalmitoylglycero-3-phosphoethanolamine (DPPE), as demonstrated by grazing-incidence X-ray-diffraction (GIXD) measurements performed on the surface of H 2 O. Lattice-controlled polycondensation within these crystallites with deuterium-enantiolabeled monomers was initiated by injecting aqueous solutions of Ag or I 2 /KI beneath the monolayers, which yielded mixtures of diastereoisomeric oligopeptides containing up to six to eight repeating units, as analyzed by MALDI-TOF mass spectrometry. Analysis of the diastereoisomeric distribution showed an enhanced relative abundance of the oligopeptides with homochiral sequences containing three or more repeating units. Within the DPPE monolayers, the nucleophilic amino group of the phospholipid operates as an initiator of polymerization at the periphery of the monomer two-dimensional crystallites. Enhanced relative abundance of enantiomerically enriched homochiral oligopeptides was obtained by the polycondensation of nonracemic monomers. This enhancement indicated a phase separation into racemic and enantiomorphous monomer crystallites within the phospholipid environment, although this separation could not be observed directly by GIXD. A possible role that might have been played by crystalline assemblies for the abiotic generation and amplification of oligopeptides with homochiral sequences is discussed.Introduction. ± One of the central enigmata in the abiotic origin of life is related to the question of how homochiral biopolymers have been formed under prebiotic conditions. An accepted scenario for early formation of biopolymers from abiotic atomic or molecular ingredients is based on the assumption that primitive polymers might have been formed on surfaces then concentrated and sequestered within primeval membrane-like films that were subsequently converted into proto-cells to form primitive vesicle-like architectures capable of engulfing the polymers for further self-replication [1 ± 3]. This scenario invokes an essential role played by early membrane-like materials in the form of primitive proto-cells. It does not, however, consider the formation of homochiral polymers from racemates or from nonracemic mixtures of activated racemic monomers of low enantiomeric imbalance within these membrane-like environments.

“Absolute” Asymmetric Polymerization within Crystalline Architectures: Relevance to the Origin of Homochirality

“…Similar results were obtained for the polymerization of nonracemic C18-Lys-TE within a phospholipid environment, where the ethanolamine group of the phospholipid served as the initiator of the reaction [25].…”

“…The polymerization of racemic monomers in ideal solutions should result in the formation of atactic polymers where the chains contain monomer residues of both enantiomers [23][24][25]. One way of generating isotactic polymers is to assemble these monomers into crystalline-like aggregates prior to the reaction; the air-water interface provides just such a medium.…”

“…A polymerization reaction within these crystallites takes place, along the glide plane, between the heterochiral The results of GIXD studies of the packing arrangement of nonracemic amphiphilic α-amino acids have shown that the latter undergo separation, either on pure water or within a monolayer of phospholipids, into a mixture of racemic and enantiomorphous domains [25,32]. Polymerization then takes place within each of the two types of crystallites, yielding syndiotactic peptides in the racemic crystallites and homochiral peptides within the enantiomorphous domains.…”

Catalysis in abiotic structured media: an approach to selective synthesis of biopolymers

“…Three structures formed by amphiphiles have been investigated for their potential in promoting peptide formation: bilayers of liposomes [68][69][70][71], micelles [46] and monolayer lattices [72,73]. As for the mineral-supported reactions, substrate monomers can be adsorbed on the amphiphile-structure surface that can easily be functionalized by mixing zwitterionic and charged amphiphiles to yield various surface charge potentials.…”

Crystalline Phase Separation of Racemic and Nonracemic Zwitterionic α‐Amino Acid Amphiphiles in a Phospholipid Environment at the Air/Water Interface: A Grazing‐Incidence X‐Ray Diffraction Study

“…± As a part of our studies on the formation of homochiral oligopeptides from nonracemic activated a-amino acid monomers, we have proposed a general mechanism for the amplification of chirality that encompasses a phase separation of the nonracemic monomers into two-dimensional (2D) crystallites, either on H 2 O or within a membrane-like environment of a phospholipid monolayer, followed by a lattice-controlled polymerization. In the preceding article of this journal issue [1], we demonstrated that polycondensation of nonracemic S-ethyl thioesters of both lysine and glutamic acid amphiphiles gives rise to homochiral oligopeptides, when embedded within a phospholipid monolayer, as determined by MALDI-TOF MS of deuteriumenantiolabeled monomers. Grazing-incidence X-ray-diffraction (GIXD) studies of the films composed of an equimolar mixture of racemic phospholipids with racemic thioesters clearly showed a phase separation between 2D crystalline domains of phospholipid and those of the thioesters, very similar to those observed for the pure components.…”