Probe Induced Folding And Regulation Of Guanine-rich DNA Structures

DNA is the main carrier for storing,replicating and transmitting genetic information.The base sequence of nucleic acid encodes structural information into biopolymers,and its structural polymorphism interacts with proteins to regulate cell biological activity.The stability of DNA structure is affected by different factors,such as the number of base pairs,the nature of bases,ionic strength,the synergistic effect of bridging double strands,the intercalation of ions and molecular substrates,etc.This thesis mainly describes the interaction between probe molecules and DNA to promote the folding and regulation of DNA structure,and constructs DNA switches and nano-components.A DNA switch is a combination of supramolecular nucleic acids,which performs a cyclic and switchable transition between two different states in the presence of appropriate inducing factors(such as pH,metal ions,ligands,photons,and electrical stimulation).In this thesis,natural small molecules are selected as probes,and DNAs containing three G-tracts are used as the research object.We have respectively developed nucleic acid switches and nano-components based on small natural drug molecules.1.A pH-triggered G-triplex switch with K⁺tolerance.In this work,we investigate the interaction between the 3'-truncated sequence of the thrombin aptamer(TBA-3t G)and the isoquinoline alkaloid(SG).A reversible switch between the imine and alkanolamine forms of a planar molecule is induced by pH to regulate the switch of the G3 structure.Isoquinoline alkaloid SG has two forms.Under acidic conditions,it exists in imine form(SG⁺).Under alkaline conditions,it exists in the form of alkanol amine(SGOH).We take the advantage of its tautomerismand use imine forms(SG⁺)as the regulator.At pH 4.9,SG⁺shows binding specificity with TBA-3t G,and this specific binding properties could trigger TBA-3t G to fold into antiparallel G3 structure.However,at pH 8.6,the regulator is converted toalkanolamine in the form of SGOH,and the G3 structure is dissociated accordingly.Reversible regulation of G3 switch is realized through the recycling of pH value.We find that the planarity of the regulator is particularly important for the construction of the G3 switch,otherwise,supramolecular host-guest encapsulation could be used to modulate pH-triggered G3 switches.Finally,we find that the G3 switch can also be optically controlled using photonic acid as a pH regulator.2.Favorable nanoassembly of G-triplex over G-quadruplex triggered by pH,oxygenand hydrogen peroxideNanoassembly of G-triplex with good reversibility induced by pH,oxygen and hydrogen peroxide.In this work,we find that a natural alkaloid of sanguinarine can serve as a tunable ligand glue to reversibly switch the dimeric G3 nanoassembly.The glue planarity is found to be a crucial factor to realize this switching.More importantly,pH,sulfite,O₂and H₂O₂can be employed as common regulators to easily modulate the glue's adhesivity for repeating the G3 assembly/disassembly with the ligand conversion between featured forms.Our work first demonstrates the higher-oder G3 nanoassembly that can be reversibly operated with the ligand's adhesivity manipulation.This provides an alternative way to understand the unique behavior of guanine-rich sequences and causes more attention to the G3 foldings since the nanoassembly event investigated herein maybe exist in living cells.