Peptidyl transfer RNA are key molecules for the biosynthesis of proteins taking place in ribosomes. In the absence of lipids synthetic amphiphilic 3'-peptidyl-RNA conjugates, molecules that mimic natural peptidyl-transfer RNA, are capable of self-assembling as vesicles in diluted aqueous solutions. In these molecules, the oligomeric folded RNA chain forms the polar ‘head group’, while suitable helix forming peptides form the hydrophobic group. Here we report on the solid support synthesis, the secondary structure analysis1and the AFM imaging2 of 3'-peptidyl-RNAs consisting of one 22-meric RNA seven base pair-hairpin mimicking the acceptor stem sequence of a tRNA connected through an amide linkage to a variety of lipophilic up to 22-meric peptides. We observed the formation of vesicles of several hundred nanometers diameter and of thick (~21 nm) supported bilayers by peptidyl-RNA on optical glass surfaces. Their strong amphiphilicity drives the conjugates to aggregate into nanovesicles and, upon concentration and 2D spreading on a glass surface, into exceptionally regular and flat supported bilayers. The structure and a model of one peptidyl-RNA molecule used in this study, Ala21RNA22, is most consistent with the flat and relatively robust bilayers of the size and homogeneicity measured by AFM 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.

Such bilayers are the first ones observed that do not contain lipids or cholesterol. We shall use these conjugates to investigate their insertion into liposomes. Peptidyl-RNA bearing a peptide sequence capable of forming pores in bacterial membranes have the potential for antibiotic activity, those bearing epitopic peptides specific for cancer cell receptors should promote cancer cell-specific endocytosis. The same compounds bear supramolecular properties that may be of interest in their application as biodegradable nano materials.

1S. Terenzi, E. Biala, N.Q. Nguyen-Trung, P. Strazewski, “Amphiphilic 3’-Peptidyl-RNA Conjugates”
Angew. Chem. 2003, 42, 3015-3018; Angew. Chem. Int. Ed. 2003, 42, 2909-2912.
2A. Lazar, A.W. Coleman, S. Terenzi, P. Strazewski, “Observation of the Formation of Supported Bilayers by Amphiphilic Peptidyl-RNA” Chem. Comm.2006, (1), 63-65.