The role of G-quadruplex structures of LIGS-generated aptamers R1.2 and R1.3 in IgM specific recognition

Int J Biol Macromol. 2019 Jul 15;133:839-849. doi: 10.1016/j.ijbiomac.2019.04.141. Epub 2019 Apr 22.

Abstract

Exploiting a variant of SELEX called "Ligand-Guided Selection" (LI-GS), we recently identified two novel truncated G-rich aptamers, called R1.2 and R1.3, specific for membrane-bound IgM (mIgM), the hallmark of B cells. Herein, the conformational behaviour of these aptamers has been analysed by multiple biophysical methods. In order to investigate their functional secondary structures, these studies have been carried out in pseudo-physiological buffers mimicking different cellular environments. Both aptamers proved to be highly polymorphic, folding into stable, unimolecular G-quadruplex structures in K+-rich buffers. In turn, in buffered solutions containing Na+/Mg2+ ions, R1.2 and R1.3 formed mainly duplex structures. Remarkably, these aptamers were able to effectively bind mIgM on B-cell lymphoma exclusively in the presence of potassium ions. These findings demonstrate the key role of G-quadruplex folding in the molecular recognition and efficient binding of R1.2 and R1.3 to mIgM expressed in lymphoma and leukemia cells, providing a precious rational basis for the design of effective aptamer-based biosensors potentially useful for the detection of cancer-relevant biomarkers.

Keywords: Aptamers; G-quadruplex; Membrane-bound IgM.

MeSH terms

  • Aptamers, Nucleotide / chemistry*
  • Aptamers, Nucleotide / metabolism*
  • Computer Simulation
  • G-Quadruplexes*
  • Humans
  • Immunoglobulin M / metabolism*

Substances

  • Aptamers, Nucleotide
  • Immunoglobulin M