Fuel-Driven Dynamic Combinatorial Peptide Libraries

12 April 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Dynamic combinatorial chemistry (DCC) creates libraries of molecules that are constantly interchanging in a dynamic combinatorial library. When a library member self-assembles, it can displace the equilibria, leading to emergent phenomena like its selection or even its replication. However, such dynamic combinatorial libraries typically operate in or close to equilibrium. This work introduces a new dynamic combinatorial chemistry fueled by a catalytic reaction cycle that forms transient, out-of-equilibrium peptide-based macrocycles. The products in this library exist out of equilibrium at the expense of fuel and are thus regulated by kinetics and thermodynamics. By creating a chemically fueled dynamic combinatorial library with the vast structural space of amino acids, we explored the liquid-liquid phase separation behavior of the library members. The new versatile chemistry enables simple and complex coacervation and creates structures with significantly longer lifetimes than other chemically fueled examples.


Dynamic combinatorial library
Liquid-liquid phase separation
Simple coacervation
Chemical reaction cycles
Chemically fueled Dynamic Combinatorial Library

Supplementary materials

Supporting Information
Supporting Information for the main text.


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