Electrostatic binding of polyanions using self-assembled multivalent (SAMul) ligand displays-structure-activity effects on DNA/heparin binding

Loryn E. Fechner, Buthaina Albanyan, Vânia M P Vieira, Erik Laurini, Paola Posocco, Sabrina Pricl*, David K. Smith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


This paper reports that modifying the ligands in self-assembled multivalent (SAMul) displays has an impact on apparent binding selectivity towards two nanoscale biological polyanions-heparin and DNA. For the nanostructures assayed here, spermidine ligands are optimal for heparin binding but spermine ligands are preferred for DNA. Probing subtle differences in such nanoscale binding interfaces is a significant challenge, and as such, several experimental binding assays-competition assays and isothermal calorimetry-are employed to confirm differences in affinity and provide thermodynamic insights. Given the dynamic nature and hierarchical binding processes involved in SAMul systems, we employed multiscale modelling to propose reasons for the origins of polyanion selectivity differences. The modelling results, when expressed in thermodynamic terms and compared with the experimental data, suggest that DNA is a shape-persistent polyanion, and selectivity originates only from ligand preferences, whereas heparin is more flexible and adaptive, and as such, actively reinforces ligand preferences. As such, this study suggests that inherent differences between polyanions may underpin subtle binding selectivity differences, and that even simple electrostatic interfaces such as these can have a degree of tunability, which has implications for biological control and regulation on the nanoscale.

Original languageEnglish
Pages (from-to)4653-4659
Number of pages7
JournalChemical Science
Issue number7
Early online date18 Apr 2016
Publication statusPublished - 1 Jul 2016

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