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

TY - JOUR

T1 - Toward Peptide Nucleic Acid (PNA) Directed Peptide Translation Using Ester Based Aminoacyl Transfer

AU - Singhal, Abhishek

AU - Bagnacani, Valentina

AU - Corradini, Roberto

AU - Nielsen, Peter E

PY - 2014/11/21

Y1 - 2014/11/21

N2 - 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.

AB - 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.

U2 - 10.1021/cb5005349

DO - 10.1021/cb5005349

M3 - Journal article

C2 - 25192412

SN - 1554-8929

VL - 9

SP - 2612

EP - 2620

JO - A C S Chemical Biology

JF - A C S Chemical Biology

IS - 11

ER -