Stacked and continuous helical self-assemblies of guanosine monophosphates detected by vibrational circular dichroism

Abstract

The aim of this study was to characterize self-assembled structures of guanosine derivatives in aqueous solutions by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD). Three guanosine derivatives were studied [5'-guanosine monophosphate (GMP), diphosphate (GDP), and triphosphate (GTP)] using a broad range of concentrations and various metal/guanosine ratios. VCD was used for the first time in this field and showed itself to be a powerful method for obtaining specific structural information in solution. It can also help to determine the impact that the cations have, when added to the solution, on the versatile structures of guanine derivatives in terms of their association and disassociation. Based on the markedly different intensities and signs of the VCD signals observed for different concentrations of guanosine derivatives, we propose various structures based on guanine quartets for high guanosine concentrations and high K(+)/guanosine ratios (i.e., columnar helical organization of the quartets, which are rearranged into a continuous helix). We performed a degenerate coupled oscillator (DCO) calculation to interpret the VCD spectra obtained and how they vary during the assembly of guanosine derivatives. The calculations correctly predicted the VCD spectra and enabled us to identify the structures of the metal cation/guanosine monophosphate aggregates. ECD in the ultraviolet region was used as a diagnostic tool to characterize the studied systems and as a contact point between the previously defined structures of the guanine derivative assemblies and the molecular systems studied here. These studies revealed that the VCD technique is a powerful new method for determining the structures of optically active guanosine motifs.

Applications of guanine quartets in nanotechnology and chemical biology

“…This includes other Xraybased techniques (for example, smallangle Xray scattering (SAXS)) 42 , along with various microscopy techniques: atomic force microscopy (AFM) was applied to charac terize the selforganization of GMP on mica 43 , SEM was applied to investigate the folding parameters and global topology of micrometrelong Na 2 (5′GMP) assemblies 36 and scanning tunnelling microscopy (STM) was applied in combination with density functional theory (DFT) calculations to assess whether and how Gquartets can be assembled on surfaces (either Au(iii) 24,44 or highly ori ented pyrolytic graphite (HOPG) 45 surface) in solventless conditions, with simple or sophisticated guanine deriva tives, in the absence or presence of Na + , K + or Ca 2+ cations. Spectroscopic techniques provided invaluable clues about Gbased selfassemblies in solution; these include Fourier transform infrared (FTIR) 46 , infrared multiple photon dissociation (IRMPD) [47][48][49] and RAMAN 50 spectroscopies, along with electronic and vibrational circular dichroism for instance (ECD 51 and VCD 52 , respectively) combined with degenerate coupled oscillator (DCO) calculations 52 and NMR 53,54 , notably diffusionordered spectroscopy (DOSY) NMR, which were successfully implemented to characterize the cationtemplated GMP aggregation in nearphysiological conditions. Finally, theoretical mod els were provided via molecular dynamics (MD) 55,56 and molecular mechanics (MM) 57 , notably for both describ ing cationtemplated Gquartet formation and simulating in silico the movement (channelling) of cation (e.g.…”

Cyclopolymerization of Disiloxane-Tethered Divinyl Monomers To Synthesize Chirality-Responsive Helical Polymers

“…), resulting in an alteration in their chiroptical properties. , Some supramolecular assemblies are also found to be chirality-responsive. For example, fibril assemblies of proteins and DNA demonstrated controlled reversal of supramolecular helical chirality dependent on pH, ionic strength, or temperature . The double helix of the oligoresorcinol nonamer formed in water was unwound by β-cyclodextrin and rewound by the addition of an adamantine .…”

Self-Assembled Nucleotide/Saccharide-Tethering Polycation-Based Nanoparticle for Targeted Tumor Therapy

“…Circular dichroism (CD) spectroscopy was used to study the conformation of self-associating GMP. In Figure S5 of the Supporting Information, GMP showed negative bands at ∼290, 280, and 250 nm, which were characteristic of a G-quartet. , Clofarabine self-assembled to produce a distinct CD signal from GMP, while Clof@GMP complex exhibited almost identical spectra to GMP. This indicated clofarabine was arranged in a similar geometric manner to GMP in Clof@GMP.…”