Solid phase synthesis of TyrT, a thymine–tyrosine conjugate with poly(A) RNA-binding ability

Abstract

The present work deals with the synthesis and characterization of a novel nucleoamino acid derivative based on a L-tyrosine moiety to which a thymine nucleobase was anchored by means of an amide bond to the N-alpha group. This derivative, denominated by us TyrT, belongs to the family of the nucleobase–amino acid conjugates that show a wide range of biological activities, frequently associated with their ability to interact with nucleic acids. In this respect, the interaction of TyrT with poly(A), a proposed RNA target for anticancer strategies, was studied by circular dichroism (CD) which suggested its ability to bind this RNA. Moreover, the modification of the morphology of a sample of TyrT in the presence of poly(A) was visualised by scanning electron microscopy (SEM) which was in agreement with the evidence that the thyminyl L-tyrosine interacts with poly(A). Finally, computational analyses have been performed to hypothesize the binding mode from a structural point of view, suggesting that the binding is mainly kept via hydrophobic contacts, reproducing a stacking-like interaction between the thymine ring of TyrT and the two successive adenine rings of a poly(A) model.