# Bivalent Surface Attachment via Cysteine Thiol Results in Efficient and Stereoselective Abiotic Peptide Synthesis

## TL;DR

Cysteine improves abiotic peptide synthesis on mineral surfaces, enabling higher yields and stereoselectivity, which could be relevant for early life and astrobiology.

## Contribution

Cysteine's bivalent surface attachment enhances stereoselective abiotic peptide synthesis, offering a novel mechanism for prebiotic chemistry.

## Key findings

- Cysteine increases surface-catalyzed peptide yields in hydrothermal vent models.
- Bivalent cysteine binding to silicates orients amino groups for stereoselective reactions.
- Thiol group reactivity boosts reaction rates and enables metal ion binding in peptides.

## Abstract

Surface-catalyzed peptide bond formation may have been
an important
source of peptides for abiogenesis, but model peptide synthesis reactions
using the consensus set of 10 abiotic amino acids give only modest
rates of peptide bond formation. Additionally, the peptides are typically
limited in length to a small number of amino acids and stereoselective
amino acid incorporation is weak or absent. An abiotic route for the
high-yield synthesis of cysteine from serine was recently reported
by Foden et al. (Science2020, 370,
865–869), indicating that, in some environments, prebiotic
cysteine may also have been available. Here, we show that the presence
of cysteine dramatically increases the yields of surface-catalyzed
peptide synthesis reactions in a hydrothermal vent solvent model containing
achiral silicate minerals and that the reaction exhibits a strong
stereoselective bias toward l-cysteine. Solid state NMR confirmed
that cysteine associates bivalently with silicates at alkaline pH
via both the carboxylate and the sulfur groups. Polarization-resolved
IRRAS indicates that the bivalent adsorption stereospecifically orients
the reactive amino group, providing a mechanism for stereoselective
incorporation of l-cysteine. Stereoselective rates of peptide
bond formation in surface-catalyzed peptide bond formation are expected
to occur for any amino acid able to form sufficiently strong side
chain–silicate interactions at alkaline pH. The high nucleophilicity
of the thiol group produces unusually high reaction rates and stereoselectivity
in such reactions, in addition to conferring transition metal ion
binding to the peptide products. The potential benefits of reactive
sulfur species for abiogenesis suggest that they may be useful biosignatures
in the search for habitable extraterrestrial environments.