biostudies-literatureLin YMinistry of EducationH2020 Marie Sklodowska-Curie ActionsFP7 People: Marie-Curie ActionsMedical Research CouncilWellcome TrustAustralian Research CouncilEngineering and Physical Sciences Research Council4034-4044https://www.ebi.ac.uk/biostudies/studies/S-EPMC7992134biostudies-literatureUnknown15(3)The evolution of life on earth eventually leads to the emergence of species with increased complexity and diversity. Similarly, evolutionary chemical space exploration in the laboratory is a key step to pursue the structural and functional diversity of supramolecular systems. Here, we present a powerful tool that enables rapid peptide diversification and employ it to expand the chemical space for supramolecular functions. Central to this strategy is the exploitation of palladium-catalyzed Suzuki-Miyaura cross-coupling reactions to direct combinatorial synthesis of peptide arrays in microtiter plates under an open atmosphere. Taking advantage of this <i>in situ</i> library design, our results unambiguously deliver a fertile platform for creating a set of intriguing peptide functions including green fluorescent protein-like peptide emitters with chemically encoded emission colors, hierarchical self-assembly into nano-objects, and macroscopic hydrogels. This work also offers opportunities for quickly surveying the diversified peptide arrays and thereby identifying the structural factors that modulate peptide properties.ACS nanoHigh-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates.PMC7992134098411/Z/12/ZDP170100511EP/M020398/1EP/K020641/1275433DP140101888MR/R015651/1660757Gelmi APashuck ETPenna MHiggins SGWojciechowski JPSpicer CDLin YYarovsky IStevens MMKim NWang STfalseHigh-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates.The evolution of life on earth eventually leads to the emergence of species with increased complexity and diversity. Similarly, evolutionary chemical space exploration in the laboratory is a key step to pursue the structural and functional diversity of supramolecular systems. Here, we present a powerful tool that enables rapid peptide diversification and employ it to expand the chemical space for supramolecular functions. Central to this strategy is the exploitation of palladium-catalyzed Suzuki-Miyaura cross-coupling reactions to direct combinatorial synthesis of peptide arrays in microtiter plates under an open atmosphere. Taking advantage of this <i>in situ</i> library design, our results unambiguously deliver a fertile platform for creating a set of intriguing peptide functions including green fluorescent protein-like peptide emitters with chemically encoded emission colors, hierarchical self-assembly into nano-objects, and macroscopic hydrogels. This work also offers opportunities for quickly surveying the diversified peptide arrays and thereby identifying the structural factors that modulate peptide properties.2021-01-01T00:00:00Z2021 Mar2025-04-04T22:00:41.418Z2025-04-04T22:00:41.418ZS-EPMC79921343358760710.1021/acsnano.0c05423