Systems chemistry of aminoacyl phosphates: Spontaneous and selective peptide oligomerisation in water driven by phase changes

07 July 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The pathways and mechanisms that allow spontaneous and selective peptide elongation in aqueous abiotic systems remain unclear. Herein we work to uncover those pathways by following the systems chemistry of aminoacyl phosphates, the synthetic counterpart of aminoacyl adenylates. Thus, oligomers up to dodecamers were synthesized in one flask and on the minute time scale, where consecutive additions activated autonomous phase changes. The resulting phases arose from the high polar and reactive nature of the aminoacyl phosphates, which can be dissolved in water in concentrations of up to 300 mM. Upon elongation, short oligomers are prevalent in solution, while in the aggregated phase, longer oligomers are selected based on their aggregation propensity. We furthermore demonstrated that the solution phases can be isolated and act as a new environment for continuous elongation, by adding various phosphates. These findings suggest that the systems chemistry of aminoacyl phosphates can activate a selection mechanism for peptide formation, by merging aqueous synthesis and self-assembly.


Systems Chemistry
Aminoacyl phosphates
Peptide Oligomerisation

Supplementary materials

Supporting Information
Materials and Methods, Synthesis, UPLC-MS analysis of libraries, microcopic characterisation of assemblies


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