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Small Sequence‐Sensitive Compounds for Specific Recognition of the G⋅C Base Pair in DNA Minor Groove
Author(s) -
Farahat Abdelbasset A.,
Guo Pu,
Shoeib Hadir,
Paul Ananya,
Boykin David W.,
Wilson W. David
Publication year - 2020
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.201904396
Subject(s) - circular dichroism , alkyl , dna , chemistry , selectivity , fluorescence , combinatorial chemistry , base pair , fluorescence spectroscopy , stereochemistry , organic chemistry , biochemistry , physics , quantum mechanics , catalysis
Abstract A series of small diamidines with thiophene and modified N ‐alkylbenzimidazole σ‐hole module represent specific binding to single G⋅C base pair (bp) DNA sequence. The variation of N‐alkyl or aromatic rings were sensitive to microstructures of the DNA minor groove. Thirteen new compounds were synthesized to test their binding affinity and selectivity. The dicyanobenzimidazoles needed to synthesize the target diamidines were made via condensation/cyclization reactions of different aldehydes with different 3‐amino‐4‐(alkyl‐ or phenyl‐amino) benzonitriles. The final diamidines were synthesized using lithium bis‐trimethylsilylamide (LiN[Si(CH 3 ) 3 ] 2 ) or Pinner methods. The newly synthesized compounds showed strong binding and selectivity to AAAGTTT compared to similar sequences AAATTT and AAAGCTTT investigated by several biophysical methods including biosensor‐SPR, fluorescence spectroscopy, DNA thermal melting, ESI‐MS spectrometry, circular dichroism, and molecular dynamics. The binding affinity results determined by fluorescence spectroscopy are in accordance with those obtained by biosensor‐SPR. These small size single G⋅C bp highly specific binders extend the compound database for future biological applications.