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Glycine to Oligoglycine via Sequential Trimetaphosphate Activation Steps in Drying Environments


Polyphosphate-mediated peptide bond formation is central to protein synthesis in modern organisms, but a simpler form of activation likely preceded the emergence of proteins and RNA. One suggested scenario involves trimetaphosphate (TP), an inorganic phosphate that promotes peptide condensation. Peptide bond formation can also be promoted by high pH and drying, but the interaction of these factors with TP has yet to be characterized kinetically. We studied the formation of glycine oligomers formed under initially alkaline conditions in the presence of TP during the process of drying. Oligopeptide products sampled over 24 h were analyzed by functionalization and high-performance liquid chromatography with ultraviolet absorption (UV-HPLC). As they dried, two different pH-dependent mechanisms dominated during different stages of the process. The first mechanism occurs in alkaline solutions and activates monomer amino acids to form dimers while reducing the pH. Our results then become consistent with a second mechanism that proceeds at neutral pH and consumes dimers to form longer products. The possibility that a series of reactions might occur where the first reaction changes the environment to favor the second, and so on, may have broader implications for prebiotic polymerization. Studying how the environment changes during time-varying conditions, like drying, could help us understand how organic polymers formed during the origin of life.

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The data shown in this study is available from J. Y. upon reasonable request.


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David Baum, Sam Gellman, Izabela Sibilska-Kaminski, and John Sutherland provided thoughtful feedback at various stages of this work.


We are grateful for funding provided by the Accelerator Program of the Wisconsin Alumni Research Foundation (WARF), the Office of the Vice Chancellor for Research and Graduate Education (OVCRGE) at the University of Wisconsin-Madison, the Common Fund of the National Institutes of Health (OT2OD030524), and the National Science Foundation (2029281, 2030750, 2151959).

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Both authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by HB. The first draft of the manuscript was written by HB and both authors contributed to subsequent versions of the manuscript.

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Correspondence to John Yin.

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The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Boigenzahn, H., Yin, J. Glycine to Oligoglycine via Sequential Trimetaphosphate Activation Steps in Drying Environments. Orig Life Evol Biosph 52, 249–261 (2022).

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  • Peptides
  • Prebiotic chemistry
  • Trimetaphosphate
  • Drying
  • Glycine
  • Condensation