Molecular Design in l‑Glutamic Acid-Based Peptide Assembly Dynamics Driven by Carbodiimide-Fueled Reaction Cycle

TL;DR

This paper shows how changing the length of alkyl chains in peptides affects their self-assembly dynamics and stability.

Contribution

The study reveals how alkyl chain length in peptides influences metastable aggregate formation and catalytic lifetimes.

Findings

Z-capped peptides with different alkyl chain lengths form metastable aggregates via intramolecular anhydride formation.

Longer alkyl chains delay structural dissolution and alter assembly dynamics.

Rational peptide design enables precise control over nanostructure properties and reaction lifetimes.

Abstract

Molecular self-assembly creates complex structures through
noncovalent
interactions. Synthetic fuel-driven systems mimic biology, yet the
effects of subtle design changes, particularly hydrophobic groups
such as alkyl chains, are still not well understood. This study showed
that the alkyl chain length critically influences the dynamic assembly
of short peptides. Z-capped peptides C3 and C6, composed of l-phenylalanine and -glutamic acid, with L-aspartic
acid as the reactive site and alkylamide groups of varying lengths
at the C-terminus, have been observed to form metastable aggregates
via intramolecular anhydride formation during a chemically fueled
reaction cycle. We elucidated that the difference in alkyl chain length
resulted in either highly dynamic assemblies or delayed structural
dissolution. Our findings provide a comprehensive understanding of
these observations, illustrating how rational peptide design enable
precise control over nanostructure properties and catalytic lifetimes.

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