The effect of linker length on binding affinity of a photoswitchable molecular glue for DNA.
Molecular glue for DNA is a small synthetic ligand that adheres two single-stranded DNAs to produce a double-stranded DNA. We previously devised a photoswitchable molecular glue (PMG) that uses external light stimuli to reversibly control DNA hybridization. To optimize the structure of PMG, we synthesized a series of PMGs and evaluated the effect of changing the methylene linker length on the binding affinity and photoresponse. From the comprehensive T(m) and CSI-TOF-MS measurements, a PMG possessing a three-methylene linker with carbamate linkage produced maximum binding affinity and photoswitching ability. These results indicate that a small difference in the linker can significantly affect PMG function. These findings are useful for designing new photoswitchable DNA-binding ligands.
Dohno
Chikara
C
Department of Regulatory Bioorganic Chemistry, The Institute of Scientific and Industrial Research (SANKEN), Osaka University, 8-1 Mihogaoka, Ibaraki 567-0047, Japan.
Uno
Shin-nosuke
SN
Sakai
Shun
S
Oku
Mika
M
Nakatani
Kazuhiko
K
D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D007536:Isomerism; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009693:Nucleic Acid Hybridization; D021241:Spectrometry, Mass, Electrospray Ionization; D013056:Spectrophotometry, Ultraviolet
D008024:Ligands; D004247:DNA