DNA-instructed acyl transfer reactions for the synthesis of bioactive peptides

Abstract

We present a method which allows for the translation of nucleic acid information into the output of molecules that interfere with disease-related protein-protein interactions. The method draws upon a nucleic acid-templated reaction, in which adjacent binding of reactive conjugates triggers the transfer of an aminoacyl or peptidyl group from a donating thioester-linked PNA-peptide hybrid to a peptide-PNA acceptor. We evaluated the influence of conjugate structures on reactivity and sequence specificity. The DNA-triggered peptide synthesis proceeded sequence specifically and showed catalytic turnover in template. The affinity of the formed peptide conjugates for the BIR3 domain of the X-linked inhibitor of apoptosis protein (XIAP) is discussed.