Enhanced stability of G-quadruplexes from conformationally constrained aep-PNA backbone

Abstract

Nucleic (DNA) acids having contiguous stretch of G sequence form quadruplex structure, which is very critical to control cell division. Recently the existence of G-quadruplex in RNA is also reported in presence of monovalent metal ion. PNA is a promising DNA analogue which binds strongly to DNA to form PNA:DNA duplex or PNA(2):DNA triplex. PNA also forms quadruplexes such G-quadruplex and i-motif in G and C-rich sequences respectively. aep-PNA containing a prolyl ring is one of several PNA analogues that provide rigidity and chirality in backbone and has binding affinity to natural DNA which is higher than that of PNA. Here we examine the ability of aep-PNA-G to form a quadruplex by UV, CD and mass spectroscopic techniques.

Influence of PNA containing 8-aza-7-deazaadenine on structure stability and binding affinity of PNA·DNA duplex: insights from thermodynamics, counter ion, hydration and molecular dynamics analysis

“…Efforts were undertaken to increase the PNAÁDNA duplex stability by chemical modification of the nucleobase as well as backbone modification. [18][19][20][21][22][23][24] Nucleobase modifications were previously reported in DNA duplexes. [25][26][27] All approaches focused either on strengthening of the H-bonds between the bases and/or increasing base-stacking interactions among them.…”

Microwave‐Assisted Synthesis of Phenylpropanoids and Coumarins: Total Synthesis of Osthol

“…num hydride (DIBAL-H) mediated reduction of the corresponding esters 3a, 3b, and 3e. The 2,3-dichloro-5,6-dicyano-1,4benzoquinone (DDQ) mediated [14] oxidation of allylic alcohols 5a-5c then yielded the desired aldehydes 6a-6c in very good yields. Again, no phenol protecting group was used within these reaction sequences.…”

“…To address this challenge, we have developed a short and versatile protecting-group-free synthetic approach for the preparation of phenylpropanoids (i.e., mainly cinnamic acid derivatives) and polyfunctionalized coumarins. [13][14][15][16] The syntheses of cinnamic acid derivatives and coumarins have been previously studied. [1c,3e,6] Unfortunately, no general approach exists to efficiently prepare cinnamic acid derivatives and coumarins by starting from the same building block (Scheme 1).…”

Neutral and Negatively Charged Phosphate Modifications Altering Thermal Stability, Kinetics of Formation and Monovalent Ion Dependence of DNA G‐Quadruplexes

“…[5][6][7][8][9] The majori-ty of studies involved nucleobase or sugar modifications, whereas alteration of phosphates was limited to commercially availablep hosphorothioates [10][11][12] and methylp hosphonates. [10] Peptiden ucleic acids (PNA) [13][14][15][16][17][18][19] including their conformationally constrained variants [20][21][22] have been investigated in the context of G4s as an example of the replacement of the entire sugar-phosphate backbone with an unnatural polyamide chain.I nvasiono fP NA strands into the native DNA [13,21,23] and RNA [24] G4 assemblies has been reported in the past, which was found to be useful for targeting G4s in cells. [25] Recent advancesi nt he modificationo ft he internucleotidic phosphate group have made available novel phosphate surrogates with variouss ubstituents at the phosphorusa tom.…”

“…The majority of studies involved nucleobase or sugar modifications, whereas alteration of phosphates was limited to commercially available phosphorothioates and methyl phosphonates . Peptide nucleic acids (PNA) including their conformationally constrained variants have been investigated in the context of G4s as an example of the replacement of the entire sugar‐phosphate backbone with an unnatural polyamide chain. Invasion of PNA strands into the native DNA and RNA G4 assemblies has been reported in the past, which was found to be useful for targeting G4s in cells .…”