Selective formation of microdroplets in model abiotic depsipeptide reactions

Sarah Fisher^a, Yishi Ezerzer^a, and Moran Frenkel-Pinter^a,b

^a Institute of Chemistry, The Hebrew University of Jerusalem, Israel 9190401

^b The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Israel 9190401

One of the most fascinating questions in the origin of life field is the driving force that led to the selection of today’s 20 universal L-alpha amino acids in biology. An essential aspect of life's emergence involves the formation of compartments, which offers encapsulation for target molecules, provides an isolated unique environment, and thereby can serve as a micro-reactor for catalysis. Assemblies also provide protection from hydrolysis in the aqueous environment. Thus, polymers with the ability to self-assemble could have an evolutionary advantage over polymers lacking this ability. We postulated that primordial peptide assembly could be one of the driving forces that led the chemical selection of alpha amino acids in life today. To test this hypothesis, we used depsipeptides, which are oligomers of amino acids and hydroxy acids that form readily under mild conditions, as model prebiotic peptides. However, it is currently 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 generated depsipeptides using a matrix of eight alpha- and beta- hydroxy acids and six alpha-, beta-, and gamma- amino acids. The reaction products were analyzed by microscopy and DLS to study assembly formation, as well as ATR-FTIR, ESI-MS, and LC-MS for chemical analysis. Preliminary results demonstrate assembly formation in some of the depsipeptide systems, and indicate a strong correlation between the identity of the hydroxy acid and the ability of the resulting depsipeptides to self-assemble.