N‑Carboxyanhydride-Mediated Fatty Acylation of Amino Acids and Peptides for Functionalization of Protocell Membranes

• Published in: Journal of the American Chemical Society 2016-12, Vol.138 (51), p.16669-16676
• Main Authors: Izgu, Enver Cagri, Björkbom, Anders, Kamat, Neha P, Lelyveld, Victor S, Zhang, Weicheng, Jia, Tony Z, Szostak, Jack W
• Format: Article
• Language: English
• Subjects: Acylation; Amino Acids - metabolism; Anhydrides - metabolism; Artificial Cells - metabolism; Cell Membrane - metabolism; Oleic Acid - metabolism; Peptides - metabolism; Phospholipids - metabolism
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.6b08801

Early protocells are likely to have arisen from the self-assembly of RNA, peptide, and lipid molecules that were generated and concentrated within geologically favorable environments on the early Earth. The reactivity of these components in a prebiotic environment that supplied sources of chemical energy could have produced additional species with properties favorable to the emergence of protocells. The geochemically plausible activation of amino acids by carbonyl sulfide has been shown to generate short peptides via the formation of cyclic amino acid N-carboxyanhydrides (NCAs). Here, we show that the polymerization of valine-NCA in the presence of fatty acids yields acylated amino acids and peptides via a mixed anhydride intermediate. Notably, N α-oleoylarginine, a product of the reaction between arginine and oleic acid in the presence of valine-NCA, partitions spontaneously into vesicle membranes and mediates the association of RNA with the vesicles. Our results suggest a potential mechanism by which activated amino acids could diversify the chemical functionality of fatty acid membranes and colocalize RNA with vesicles during the formation of early protocells.