Abstract
This manuscript reports the molecular basis for double-stranded DNA (dsDNA) binding of hairpin polyamides incorporating a 5-alkyl thiazole (Nt) unit. Hairpin polyamides containing an N-terminal Nt unit induce higher melting stabilisation of target dsDNA sequences relative to an archetypical hairpin polyamide incorporating an N-terminal imidazole (Im) unit. However, modification of the N-terminus from Im to Nt-building blocks results in an increase in dsDNA binding affinity but lower G-selectivity. A general G-selectivity trend is observed for Nt-containing polyamide analogues. G-selectivity increases as the steric bulk in the Nt 5-position increases. Solution-based NMR structural studies reveal differences in the modulation of the target DNA duplex of Nt-containing hairpin polyamides relative to the Im-containing archetype. A structural hallmark of an Nt polyamide•dsDNA complex is a more significant degree of major groove compression of the target dsDNA sequence relative to the Im-containing hairpin polyamide.
Original language | English |
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Pages (from-to) | 42-53 |
Number of pages | 12 |
Journal | Nucleic Acids Research |
Volume | 46 |
Issue number | 1 |
Early online date | 29 Nov 2017 |
DOIs | |
Publication status | Published - 9 Jan 2018 |
Keywords
- hairpin polyamides
- double-stranded DNA (dsDNA)
- dsDNA binding