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Design and Synthesis of Cyclic Mismatch‐Binding Ligands (CMBLs) with Variable Linkers by Ring‐Closing Metathesis and their Photophysical and DNA Repeat Binding Properties
Author(s) -
Mukherjee Sanjukta,
Dohno Chikara,
Nakatani Kazuhiko
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201702064
Subject(s) - linker , chemistry , circular dichroism , stereochemistry , fluorescence , metathesis , crystallography , monomer , surface plasmon resonance , polymer , materials science , organic chemistry , polymerization , physics , quantum mechanics , computer science , nanoparticle , nanotechnology , operating system
Cyclophane‐containing bis(2‐amino‐1,8‐naphthyridine) moieties attached to variable linkers at the C2‐position (linker B) were synthesized as cyclic mismatch‐binding ligands (CMBLs). Ring‐closing metathesis (RCM) is used as a key step for the introduction of double bonds at the linker B. Decreasing the size of the linker of the substrate, formation of the RCM products with an increasing trans / cis ( E / Z ) ratio was observed with moderate to high overall yields. Concentration‐dependent fluorescence spectra were observed for CMBLs with longer linkers ( n =3), whereas concentration‐independent spectra were observed for CMBLs with shorter linkers ( n =2 and/or 1) with a marked exception of the E ‐alkene 6 a . Concomitant changes in the absorption as well as in the fluorescence spectra were also observed for the CMBLs with an increasing hydrophobicity of the solvent. Absorption and fluorescence spectra of the CMBLs in solutions containing 99–100 % methanol resembled to that of the monomer . The binding behavior of these CMBLs with repeat DNA structures was investigated by using a surface plasmon resonance (SPR) assay and circular dichroism (CD) spectra. The cyclic E ‐alkenes 1 a ( n =3) and 3 a ( n =2) show an orthogonal binding relationship with d(CCTG) 9 and d(CAG) 9 . However, the selectivity for the cyclic Z ‐alkenes increased with decreasing the length of the linker from compound 2 b ( n =3) to compound 7 b ( n =1). These compounds display a large molecular diversity, which allowed the tuning of the binding affinity and selectivity of the CMBLs by varying the linkers towards various biologically significant repeat DNA structures.