Water-Based Dynamic Depsipeptide Chemistry: Building Block Recycling and Oligomer Distribution Control Using Hydration-Dehydration Cycles.

Autor:	C M; School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States., Frenkel-Pinter M; School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States., Smith KH; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Rivera-Santana VF; Department of Chemistry, University of Puerto Rico, Mayagüez, Puerto Rico 00681, United States., Sargon AB; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Jacobson KC; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Guzman-Martinez A; Department of Chemistry, University of Puerto Rico, Mayagüez, Puerto Rico 00681, United States., Williams LD; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Leman LJ; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States., Liotta CL; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Grover MA; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, United States., Hud NV; NSF/NASA Center for Chemical Evolution, Atlanta, Georgia 30332, United States.; School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, United States.
Jazyk:	angličtina
Zdroj:	JACS Au [JACS Au] 2022 May 17; Vol. 2 (6), pp. 1395-1404. Date of Electronic Publication: 2022 May 17 (Print Publication: 2022).
DOI:	10.1021/jacsau.2c00087
Abstrakt:	The high kinetic barrier to amide bond formation has historically placed narrow constraints on its utility in reversible chemistry applications. Slow kinetics has limited the use of amides for the generation of diverse combinatorial libraries and selection of target molecules. Current strategies for peptide-based dynamic chemistries require the use of nonpolar co-solvents or catalysts or the incorporation of functional groups that facilitate dynamic chemistry between peptides. In light of these limitations, we explored the use of depsipeptides: biorelevant copolymers of amino and hydroxy acids that would circumvent the challenges associated with dynamic peptide chemistry. Here, we describe a model system of N -(α-hydroxyacyl)-amino acid building blocks that reversibly polymerize to form depsipeptides when subjected to two-step evaporation-rehydration cycling under moderate conditions. The hydroxyl groups of these units allow for dynamic ester chemistry between short peptide segments through unmodified carboxyl termini. Selective recycling of building blocks is achieved by exploiting the differential hydrolytic lifetimes of depsipeptide amide and ester bonds, which we show are controllable by adjusting the solution pH, temperature, and time as well as the building blocks' side chains. We demonstrate that the polymerization and breakdown of the depsipeptides are facilitated by cyclic morpholinedione intermediates, and further show how structural properties dictate half-lives and product oligomer distributions using multifunctional building blocks. These results establish a cyclic mode of ester-based reversible depsipeptide formation that temporally separates the polymerization and depolymerization steps for the building blocks and may have implications for prebiotic polymer chemical evolution. Competing Interests: The authors declare no competing financial interest. (© 2022 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu