Affiliation:
1. Department of Pharmaceutical and Pharmacological Science University of Padua Via Marzolo 5 35131 Padua Italy
2. Slovenian NMR Centre National Institute of Chemistry Hajdrihova 19 1000 Ljubljana Slovenia
Abstract
AbstractDNA sequences containing at least four runs of repetitive cytosines can fold into tetra‐helical structures called i‐Motifs (iMs). The interest in these DNA secondary structures is increasing due to their therapeutical and technological applications. Still, limited knowledge of their folding requirements is currently available. We developed a novel step‐by‐step pipeline for the systematic screening of putative iM‐forming model sequences. Focusing on structures comprising only three cytosine‐cytosine+ base pairs, we investigated what the minimal lengths of the loops required for formation of an intra‐molecular iM are. Our data indicate that two and three nucleotides are required to connect the strands through the minor and majorgrooves of the iM, respectively. Additionally, they highlight an asymmetric behavior according to the distribution of the cytosines. Specifically, no sequence containing a single cytosine in the first and third run was able to fold into intra‐molecular iMs with the same stability of those formed when the first and the third run comprise two cytosines. This knowledge represents a step forward toward the development of prediction tools for the proper identification of biologically functional iMs, as well as for the rational design of these secondary structures as technological devices.
Funder
Associazione Italiana per la Ricerca sul Cancro
Fondazione Cassa di Risparmio di Padova e Rovigo
European Commission
Central European Research Infrastructure Consortium
Javna Agencija za Raziskovalno Dejavnost RS