Enantiopurity‐Dependent Peptide Coacervates and Asymmetric Organocatalysis
Year: 2026
Type: article
Abstract: ABSTRACT Membraneless compartmentalization via liquid–liquid phase separation (LLPS) has emerged as a powerful strategy to organize biochemical reactions. Recently, peptide‐based coacervates demonstrated the potential to function as microreactors by enhancing reaction kinetics through increased local concentrations and altered microenvironments. Here, we introduce an O‐methylated diphenylalanine‐based tripeptide LLL PFF‐OCH 3 containing an N‐terminal proline, designed to undergo LLPS, and simultaneously function as an enantioselective organocatalyst. Comprehensive characterization via confocal microscopy, fluorescence recovery after photobleaching (FRAP), micro‐Raman and attenuated total reflection infrared (ATR‐IR) spectroscopy, diffusion‐surface plasmon resonance ( D ‐SPR), and molecular dynamics (MD) simulations revealed the formation of stable liquid droplets. In contrast, a racemic mixture of LLL PFF‐OCH 3 and DDD PFF‐OCH 3 failed to form liquid droplets and instead formed a solid precipitate, unveiling a critical role of enantiopurity in LLPS. Proof‐of‐concept catalytic studies proved enantioselective organocatalytic activity of the LLL PFF‐OCH 3 liquid coacervates. Beyond catalysis these results may have broader implications in understanding prebiotic chemistry and neurodegeneration.
Source: Small
Authors: Alice Vetrano, Nico di Fonte, Olivier Monasson, Federico Perrella, Martina Porco, Ferdinando Mercuri, Gianluca Dell'Orletta, Francesco Petragnano, Alessio Carioscia, Davide Deodato, Damiano Calcagno, Giovanna Salvitti, Samantha Reale, Fabio Pesciaioli, Carino Ferrante, Davide Tedeschi, Giuseppe Grasso, Paola Benassi, Elisa Peroni, Armando Carlone, Isabella Daidone, Claudio Iacobucci
Institutions: University of L'Aquila, Centre National de la Recherche Scientifique, Université Paris-Saclay, CY Cergy Paris Université, Biomolécules : Conception, Isolement, Synthèse, National Interuniversity Consortium of Materials Science and Technology, University of Catania, Fondazione G.B. Bietti
Language: English
Subfield: Biomaterials
Field: Materials Science
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $5,790
Funders: European Commission, NextGenerationEU
OpenAlex ID: W7128817249