Self-Assembly of Dendritic Dipeptides as a Model of Chiral Selection in Primitive Biological Systems

Abstract

Biological macromolecules are homochiral, composed of sequences of stereocenters possessing the same repeated absolute configuration. This chapter addresses the mechanism of homochiral selection in polypeptides. In particular, the relationship between the stereochemistry (L or D) of structurally distinct α-amino acids is explored. Through functionalization of Tyr-Xaa dipeptides with self-assembling dendrons, the effect of stereochemical sequence of the dipeptide on the thermodynamics of self-assembly and the resulting structural features can be quantified. The dendritic dipeptide approach effectively isolates the stereochemical information of the shortest sequence of stereochemical information possible in polypeptide, while simultaneously allowing for dendron driven tertiary and quaternary structure formation and subsequent transfer of chiral information from the dipeptide to the dendritic sheath. This approach elucidates a mechanism of selecting a homochiral relationship between dissimilar but neighboring α-amino acids through thermodynamic preference for homochirality in solution-phase and bulk supramolecular helical polymerization.

Inversion of Supramolecular Chirality by Sonication-Induced Organogelation

“…Recently, Conejero-Muriel et al have demonstrated the effect of the supramolecular chirality of short peptide hydrogels on protein crystallogenesis 31 . Moreover, the effects of solvents and the participation of chiral guests on the supramolecular chirality of peptide-based organogelators were reported previously 32 33 34 35 . Here, we report, for the first time, the inversion of chirality by fluorinated peptide-based gelators that contain two fluorine atoms, upon sonication-induced organogelation.…”

Extraordinary Acceleration of Cogwheel Helical Self-Organization of Dendronized Perylene Bisimides by the Dendron Sequence Encoding Their Tertiary Structure

“…12 Supramolecular deracemization does not occur in systems with strong intermolecular interactions, such as chiral dendritic dipeptides, 13 which instead give lower order assemblies when not enantiopure. 14 Indeed, incomplete deracemization of mixtures of hat-shaped molecules containing inseparable, diastereomeric combinations of stereocenters gave reduced order in the crystal state. This observation is analogous to the amorphous nature of atactic poly(propylene) compared to the crystallinity of its isotactic counterpart.…”

“…The mechanism of deracemization, which depended on weak interactions between individual molecules, could only be understood using solid-state NMR . Supramolecular deracemization does not occur in systems with strong intermolecular interactions, such as chiral dendritic dipeptides, which instead give lower order assemblies when not enantiopure . Indeed, incomplete deracemization of mixtures of hat-shaped molecules containing inseparable, diastereomeric combinations of stereocenters gave reduced order in the crystal state.…”

Peptide–dendron hybrids that adopt sequence-encoded β-sheet conformations

“…Greater control over molecular structure can be gained by combining peptides with dendrons 20, 21 or other sequence-defined polymers. The diverse pool of α-amino acid monomers can enrich the programmable functionality of dendrons by conferring chirality, 22–24 molecular recognition, 25 surface adsorption, 26 and stimulus responsive properties 27–33 to peptide-dendron hybrids. The homogeneity of hybrids obtained from monodisperse polymers may be advantageous for applications as therapeutics.…”