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

Abstract

AbstractRacemic S‐ethyl thioesters of Nε‐stearoyllysine (= S‐ethyl (R,S)‐2‐amino‐6‐(stearoylamino)hexanethioate) and S‐ethyl thioesters of γ‐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 H2O. Lattice‐controlled polycondensation within these crystallites with deuterium‐enantiolabeled monomers was initiated by injecting aqueous solutions of Ag+ or I2/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.