Adina Lazar, Anthony Coleman, Silvia Terenzi, and Peter Strazewski Chemical Communications 2006, (1), 63-65 Observation of the Formation of Supported Bilayers by Amphiphilic Peptidyl-RNA Amphiphilic peptidyl-RNA are likely to have played an important role at the origin of RNA-controlled peptide synthesis that could have taken place in lipidic bilayer vesicles. Largely lipophilic peptides would have served as primordial molecular anchoring devices that enabled their RNA carriers to be transiently immobilized, compartmentalized and thus highly concentrated on or in liposomes. In the absence of lipids synthetic amphiphilic peptidyl-RNA conjugates, molecules that mimic natural peptidyl-transfer RNA, are capable of self-assembling on glass substrates as vesicules and supported bilayers. In these molecules, the oligomeric folded RNA chain forms the polar `head group', while suitable helix forming peptides form the hydrophobic group. In the present communication we report on the observation of the formation of vesicles of several hundred nanometers diameter and of thick (about 21 nm) supported bilayers by peptidyl-RNA on optical glass surfaces. The structure and a model of the peptidyl-RNA molecule, Ala21RNA22, used in this study is most consistent with the flat and relatively robust bilayers of the size and homogeneicity measured by atomic force microscopy if a rearrangement from the alpha-helical conformation of the peptide, as was spectroscopically observed in solution, into beta-sheets within the layered structure is assumed.