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

TY - JOUR

T1 - Electrostatic binding of polyanions using self-assembled multivalent (SAMul) ligand displays-structure-activity effects on DNA/heparin binding

AU - Fechner, Loryn E.

AU - Albanyan, Buthaina

AU - Vieira, Vânia M P

AU - Laurini, Erik

AU - Posocco, Paola

AU - Pricl, Sabrina

AU - Smith, David K.

N1 - © The Royal Society of Chemistry 2016. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

PY - 2016/7/1

Y1 - 2016/7/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84976317078&partnerID=8YFLogxK

U2 - 10.1039/c5sc04801j

DO - 10.1039/c5sc04801j

M3 - Article

AN - SCOPUS:84976317078

SN - 2041-6520

VL - 7

SP - 4653

EP - 4659

JO - Chemical Science

JF - Chemical Science

IS - 7

ER -