High-Throughput Peptide Derivatization toward Supramolecular Diversification in Microtiter Plates.

Yiyang Lin,Christopher D Spicer,Stuart G Higgins,Molly M Stevens,Irene Yarovsky,Jonathan P Wojciechowski,E Thomas Pashuck,Amy Gelmi,Nayoung Kim,Shih-Ting Wang,Matthew Penna

doi:10.1021/acsnano.0c05423

Yiyang Lin, Christopher D Spicer + Show 9 more

Open Access

https://doi.org/10.1021/acsnano.0c05423

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Abstract

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 in situ 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.

Highlights

The evolution of life on earth eventually leads to the emergence of species with increased complexity and diversity
In the presence of sodium palladium chloride (Na2PdCl4) as a catalyst, P0 efficiently reacted with a series of arylboronates via Suzuki−Miyaura cross coupling in aqueous solution and transformed into the corresponding biaryl derivatives
We studied the supramolecular self-assembly of tripeptide products from Suzuki−Miyaura cross coupling by fluorescence assays, transmission electron microscopy (TEM), atomic force microscopy (AFM), and circular dichroism (CD)

Summary

Introduction

The evolution of life on earth eventually leads to the emergence of species with increased complexity and diversity. 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 crosscoupling reactions to direct combinatorial synthesis of peptide arrays in microtiter plates under an open atmosphere. One example is polypeptide diversification through sequence engineering with the combinations of 20 canonical amino acids, which provides a variety of structures and functions across different dimensions.[1−8] Additional complexity and added benefits (e.g., molecular fluorescence, biological activity, site-specific modification, and strengthened aggregation propensity) can be achieved through synthetically incorporating unnatural amino acids or functional groups.[9−17] Such a chemical approach to obtain peptide diversification is usually associated with tedious organic synthesis. We demonstrate the general utility to discover unnatural peptide sets and identify the chemical elements determining their behaviors such as microscopic self-assembly and macroscopic hydrogelation as well as chemically encoded fluorescent nanostructures

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