title: N-Carboxyanhydride-Mediated Fatty Acylation of Amino Acids and Peptides for Functionalization of Protocell Membranes.
abstract: 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, Nα-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.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
authors.forename: Enver Cagri
authors.identifier: 0000-0001-6673-3635
authors.initials: EC
authors.lastname: Izgu
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.|Department of Biosciences, Åbo Akademi University , Åbo FI-20520, Finland.
authors.forename: Anders
authors.initials: A
authors.lastname: Björkbom
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
authors.forename: Neha P
authors.initials: NP
authors.lastname: Kamat
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.
authors.forename: Victor S
authors.initials: VS
authors.lastname: Lelyveld
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.|Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Weicheng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.|Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Tony Z
authors.initials: TZ
authors.lastname: Jia
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital , 185 Cambridge Street, Boston, Massachusetts 02114, United States.|Department of Genetics, Harvard Medical School , 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, United States.|Department of Chemistry and Chemical Biology, Harvard University , 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Szostak
mesh_terms: D000215:Acylation; D000596:Amino Acids / Q000378:metabolism*; D000812:Anhydrides / Q000378:metabolism*; D058045:Artificial Cells / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D019301:Oleic Acid / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism
chemical_list: D000596:Amino Acids; D000812:Anhydrides; D010455:Peptides; D010743:Phospholipids; D019301:Oleic Acid