Double-degradable responsive self-assembled multivalent arrays-temporary nanoscale recognition between dendrons and DNA

TY - JOUR

T1 - Double-degradable responsive self-assembled multivalent arrays-temporary nanoscale recognition between dendrons and DNA

AU - Barnard, A.

AU - Posocco, P.

AU - Fermeglia, M.

AU - Tschiche, A.

AU - Calderon, Marcelo

AU - Pricl, S.

AU - Smith, D.K.

N1 - © Royal Society of Chemistry 2014. This is an author produced version of a paper accepted for publication in Organic & Biomolecular Chemistry. Uploaded in accordance with the publisher's self-archiving policy.

PY - 2014/1/21

Y1 - 2014/1/21

N2 - This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA-this can be simulated by multiscale modelling. Incorporation of an S-S linkage between the multivalent hydrophilic dendron and the hydrophobic units responsible for self-assembly allows these structures to undergo triggered reductive cleavage, with dithiothreitol (DTT) inducing controlled breakdown, enabling the release of bound DNA. As such, the high-affinity self-assembled multivalent binding is temporary. Furthermore, because the multivalent dendrons are constructed from esters, a second slow degradation step causes further breakdown of these structures. This two-step double-degradation mechanism converts a large self-assembling unit with high affinity for DNA into small units with no measurable binding affinity-demonstrating the advantage of self-assembled multivalency (SAMul) in achieving highly responsive nanoscale binding of biological targets.

AB - This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA-this can be simulated by multiscale modelling. Incorporation of an S-S linkage between the multivalent hydrophilic dendron and the hydrophobic units responsible for self-assembly allows these structures to undergo triggered reductive cleavage, with dithiothreitol (DTT) inducing controlled breakdown, enabling the release of bound DNA. As such, the high-affinity self-assembled multivalent binding is temporary. Furthermore, because the multivalent dendrons are constructed from esters, a second slow degradation step causes further breakdown of these structures. This two-step double-degradation mechanism converts a large self-assembling unit with high affinity for DNA into small units with no measurable binding affinity-demonstrating the advantage of self-assembled multivalency (SAMul) in achieving highly responsive nanoscale binding of biological targets.

UR - http://www.scopus.com/inward/record.url?scp=84890290308&partnerID=8YFLogxK

U2 - 10.1039/c3ob42202j

DO - 10.1039/c3ob42202j

M3 - Article

AN - SCOPUS:84890290308

SN - 1477-0520

VL - 12

SP - 446

EP - 455

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

IS - 3

ER -