Insect multimeric G-quadruplexes fold into antiparallel structures of different compactness and stability in K+ and Na+ solutions

Abstract

Human telomere sequences (TTAGGG)_n fold into G-quadruplexes with different conformations in K⁺ and Na⁺ solutions, which are highlighted for their potential as antitumor drug targets. Moreover, human multimeric G-quadruplexes have been broadly studied potentially for screening ligands with higher selectivity than monomeric G-quadruplexes. Most insects have telomeres consisting of pentanucleotide (TTAGG) repeats, which fold into an antiparallel structured G-quadruplex with a two-layer G-planar in a K⁺ solution. However, the structure of insect telomeric G-quadruplexes in Na⁺ solutions and their higher-order structures have not been explored. The quinoline derivative BMPQ-1 has been reported to bind human multimeric G-quadruplex. This study compared the stability and compactness of insect monomeric and multimeric G-quadruplex structures in K⁺ and Na⁺ solutions and further validated the interaction between BMPQ-1 and insect multimeric G-quadruplexes. Circular dichroism (CD) spectral scanning analysis revealed that although the insect telomeric G-quadruplex folds into an antiparallel structure in both K⁺ and Na⁺ solutions, all the insect telomeric G-quadruplexes are more stable in Na⁺ solutions. Fluorescence resonance energy transfer (FRET) analysis indicated insect telomeric G-quadruplexes have a more compact structure in Na⁺ solutions. BMPQ-1 exhibited higher selectivity for insect multimeric G-quadruplex Bom37 than monomeric G-quadruplex Bom17, and had a different binding pattern to Bom37 G-quadruplex in K⁺ and Na⁺ solutions. Finally, BMPQ-1 was found to have a significant inhibitory effect on the proliferation of pest cells. This study contributes to our comprehensive understanding of insect telomeric G-quadruplexes.