Dec 3, 2016

C 3-symmetric opioid scaffolds are pH-responsive DNA condensation agents

Nucleic Acids Research
Natasha McStayAndrew Kellett

Abstract

Herein we report the synthesis of tripodal C3-symmetric opioid scaffolds as high-affinity condensation agents of duplex DNA. Condensation was achieved on both supercoiled and canonical B-DNA structures and identified by agarose electrophoresis, viscosity, turbidity and atomic force microscopy (AFM) measurements. Structurally, the requirement of a tris-opioid scaffold for condensation is demonstrated as both di- (C2-symmetric) and mono-substituted (C1-symmetric) mesitylene-linked opioid derivatives poorly coordinate dsDNA. Condensation, observed by toroidal and globule AFM aggregation, arises from surface-binding ionic interactions between protonated, cationic, tertiary amine groups on the opioid skeleton and the phosphate nucleic acid backbone. Indeed, by converting the 6-hydroxyl group of C3-morphine ( MC3: ) to methoxy substituents in C3-heterocodeine ( HC3: ) and C3-oripavine ( OC3: ) molecules, dsDNA compaction is retained thus negating the possibility of phosphate-hydroxyl surface-binding. Tripodal opioid condensation was identified as pH dependent and strongly influenced by ionic strength with further evidence of cationic amine-phosphate backbone coordination arising from thermal melting analysis and circular dichroism sp...Continue Reading

Mentioned in this Paper

Guanosine
Oripavine
Guar hydroxypropyltrimonium (1.7 substituents per saccharide)
Mesitylene
Deoxyribonuclease I
Amines
Derivatives
Tertiary amines, anticholinergic
Electrophoresis, Agar Gel
Endodeoxyribonuclease SalI

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