Toward Peptide Nucleic Acid (PNA) Directed Peptide Translation Using Ester Based Aminoacyl Transfer

Abstract

Peptide synthesis is a fundamental feature of life. However, it still remains unclear how the contemporary translation apparatus evolved from primitive prebiotic systems and at which stage of the evolution peptide synthesis emerged. Using simple molecular architectures, in which aminoacyl transfer of phenylalanine occurs either between two ends of a PNA stem loop structure, between two PNAs in a duplex, or between two PNAs assembled on a PNA template, we show that bona fide template instructed phenylalanine transfer can take place. Thus, we have identified conditions which allow template assisted intermolecular aminoacyl transfer using simple ester aminolysis chemistry primitively analogous to the ribosomal peptidyl transferase reaction in the absence of anchimeric assistance from ribose and ribosome catalysis. These results help define the minimum chemical boundary conditions for the translation process and also give insight into the possibilities for the prebiotic emergence of RNA-independent translation.

Programmable Nucleic Acid Nanoswitches for the Rapid, Single-Step Detection of Antibodies in Bodily Fluids

“…In this case the antigen-conjugated strand is made of peptide-nucleic acid (PNA), a DNA mimic that, while still maintaining a high sequence specificity towards DNA complementary strands, has a pseudopeptide backbone which makes the conjugation with peptides easier. 23 The modular nature of such approach renders it easily applicable to the detection of different antibodies through the simple expedient of changing only the strand #2 (antigen-conjugated strand). With this new modular and versatile approach we have first employed as recognition element a 12-residue long HIV-1-p17 epitope (p17) recognizing the anti-HIV-1 p17 antibody ( Figure 4b).…”

Small and Random Peptides: An Unexplored Reservoir of Potentially Functional Primitive Organocatalysts. The Case of Seryl-Histidine

“…It is an example of something that has been dubbed ‘supramolecular selection’, a process that operates in the prebiotic ecology stage of prebiotic evolution and ensures the selection of certain macromolecular assemblies over others [91]. Finally, it should be mentioned that in another study, Ser-His was employed to promote peptide bond formation between two groups linked to the ends of a synthetic PNA stem loop structure [92], but in this case, its effectiveness as an organocatalyst was poor.…”

Visible-light triggered templated ligation on surface using furan-modified PNAs

“…The eld of oligonucleotide-templated reactions features many applications of PNA systems, as evidenced by the large number of templated reactions and ligations reported in literature (i.e., carrier release, [18][19][20] in cellulo and in vivo nucleic acid imaging, 17,21 developments of lateral ow devices for RNA detection, 22,23 uorogenic reactions, 10,12,[24][25][26][27] catalytic and autocatalytic systems, 14,[28][29][30][31][32] detection and targeting of oligonucleotides involved in genetic-based diseases, 15,33,34 articial aminoacyl transferases and peptide ligation [35][36][37][38][39] ). Oligonucleotide templated reactions, in a wider perspective, have also been explored in the eld of nanotechnology.…”