title: Kinetics of prebiotic depsipeptide formation from the ester-amide exchange reaction.
abstract: In this work, we introduce a kinetic model to study the effectiveness of ester-mediated amide bond formation under prebiotic conditions. In our previous work, we found that a simple system composed of α-hydroxy acids and α-amino acids is capable of forming peptide bonds via esterification followed by the ester-amide exchange reaction. To further understand the kinetic behavior of this copolymerization, we first tracked the growth of initial species from a valine/lactic acid mixture in a closed system reactor. A mathematical model was developed to simulate the reactions and evaluate the rate constants at different temperatures. We found these reactions can be described by the empirical Arrhenius equation even when reaction occurred in the solid (dry) state. Further calculations for activation parameters showed that the ester-mediated pathway facilitates amide bond formation by lowering activation entropies. These results provide a theoretical framework that illustrates why the ester-mediated pathway for peptide bond formation is efficient and why it would have been more favorable on the early Earth, compared to peptide bond formation without the aid of hydroxy acids.
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA. martha.grover@chbe.gatech.edu and NSF/NASA Center for Chemical Evolution, USA.
authors.forename: Sheng-Sheng
authors.initials: SS
authors.lastname: Yu
authors.affiliation: NSF/NASA Center for Chemical Evolution, USA and Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Ramanarayanan
authors.initials: R
authors.lastname: Krishnamurthy
authors.affiliation: NSF/NASA Center for Chemical Evolution, USA and School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Facundo M
authors.initials: FM
authors.lastname: Fernández
authors.affiliation: NSF/NASA Center for Chemical Evolution, USA and School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Hud
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA. martha.grover@chbe.gatech.edu and NSF/NASA Center for Chemical Evolution, USA.
authors.forename: F Joseph
authors.initials: FJ
authors.lastname: Schork
authors.affiliation: School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA. martha.grover@chbe.gatech.edu and NSF/NASA Center for Chemical Evolution, USA.
authors.forename: Martha A
authors.initials: MA
authors.lastname: Grover