5oe1

Publication Abstract from PubMed

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.

Structural basis of DNA duplex distortion induced by thiazole-containing hairpin polyamides.,Padroni G, Parkinson JA, Fox KR, Burley GA Nucleic Acids Res. 2017 Nov 29. pii: 4670956. doi: 10.1093/nar/gkx1211. PMID:29194552^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.