06 Oct Hebrew University Study Demonstrates That a Small Subset of Amino Acids Can Self Assemble, Possibly Leading to Early Life on Earth

Self Assembly of Subset of Amino Acids May Have Led to First Life

MedicalResearch.com Interview with:

Dr. Frenkel-Pinter

Dr. Moran Frenkel-Pinter Ph.D.
Senior Lecturer (assistant professor)
Institute of Chemistry
Hebrew University of Jerusalem
Member of the NASA Center for the Origins of Life

MedicalResearch.com: What is the background for this study? What is unique about the 20 amino acids found in living organisms?

Response: One of the most fascinating mysteries in the field of origins of life concerns the driving force that led to the selection of today’s 20 universal L-alpha amino acids in biology. Out of hundreds and possibly thousands of amino acids that were present on the prebiotic Earth, only a small subset was selected for biology. An essential aspect of life’s emergence involves the formation of compartments, which offer encapsulation for target molecules and provide protection from degradation in water.

We postulated that primordial peptide assembly could be one of the driving forces that led to the chemical selection of alpha amino acids in life today. To test this hypothesis, we generated depsipeptides, oligomers composed of ester bonds and peptide bonds that form readily under mild drying conditions, as model prebiotic peptides. However, it was unknown whether depsipeptides form assemblies in an aqueous environment similarly to peptides and proteins. To test the hypothesis that depsipeptides with alpha backbones will form assemblies more readily than beta backbones, we synthesized depsipeptides using a matrix of alpha- and beta- hydroxy acids and alpha-, beta-, and gamma- amino acids. Our results demonstrate assembly formation in depsipeptide systems containing hydrophobic hydroxy acids and indicate that depsipeptides containing alpha hydroxy acid backbones are significantly more stable than beta analogs. Overall, our results offer an assembly-driven mode of selection for the alpha backbone in present-day biology.

MedicalResearch.com: Are these amino acids found on comets or asteroids?

Response:  We used simple amino acids that are found in meteorites. It is well established that prebiotic Earth contained a rich variety of amino acid isomers, including alpha, beta, and gamma amino acids. These amino acids originated from both exogenous deliveries, as indicated by traces found on meteorites, as well as endogenous synthesis on prebiotic Earth. Notably, not all proteinogenic amino acids are found in meteorites and model prebiotic reactions, but rather only 10 early amino acids out of the 20 proteinogenic amino acids. In addition, there are many other non-proteinogenic amino acids that are found in meteorites and model prebiotic reactions, such as beta- and gamma- amino acids. In this paper we addressed the question of why alpha amino acids were selected over longer backbone analogs that were prebiotically available.  

MedicalResearch.com: What should readers take away from your report?

Response: Overall, this study sheds light on the unique structural and chemical properties of alpha backbones as critical factors in the early stages of life’s proto-peptide evolution. The prolonged physical stability through self-assembly of alpha depsipeptides suggests that these structures were well suited for further complexification of chemical species during chemical evolution. Our results suggest a possible assembly-driven selection mechanism for the fittest molecules during chemical evolution, which may have led to the emergence of the first protocells. Together, these findings support the hypothesis that the predominance of alpha amino acids in modern biology may have originated from their superior ability to form the physically stable, compartment-like structures essential for the development of early life.

MedicalResearch.com: What recommendations do you have for future research as a results of this study?

Response: It will be interesting in the future to explore the vast sequence-structure space using additional amino acids. Moreover, it will be interesting to explore whether chirality affects the assembly using hydrophobic amino acids as building blocks. Moreover, it is yet to be determined whether such structures could serve as compartments and eventually evolve into functioning protocells.

MedicalResearch.com: Is there anything else you would like to add?

Response: We demonstrate here, for the first time, the ability of depsipeptide, which is a model proto-peptide, to self-assemble, similar to modern peptides.

Citation:
S. Fisher, Y. Ezerzer, R. Edri, D. Akulenko, E. Marland, & M. Frenkel-Pinter,
Protopeptide backbone affects assembly in aqueous solutions, Proc. Natl. Acad. Sci. U.S.A. 122 (40) e2500503122,
https://doi.org/10.1073/pnas.2500503122 (2025).

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Last Updated on October 6, 2025 by Marie Benz MD FAAD