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

Chemical Science
Loryn E FechnerDavid K Smith

Abstract

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 ...Continue Reading

References

Jul 1, 1978·Journal of Medicinal Chemistry·B F CainW A Denny
Jan 1, 1987·The Biochemical Journal·K IshiiT Andoh
Jun 21, 2001·Journal of the American Chemical Society·D L BogerM P Hedrick
Apr 17, 2003·Angewandte Chemie·Derk JoesterFrançois Diederich
May 15, 2004·Molecular & Cellular Proteomics : MCP·LaToya S JonesC Russell Middaugh
Nov 17, 2005·Journal of the American Chemical Society·Byung-Sun KimMyongsoo Lee
Sep 14, 2006·Nano Letters·Kanya RajangamSamuel I Stupp
Jan 15, 2009·Angewandte Chemie·Kristina RiehemannHarald Fuchs
Mar 19, 2009·Angewandte Chemie·Marion K Müller, Luc Brunsveld
May 26, 2009·Advances in Colloid and Interface Science·Ksenija Kogej
May 28, 2009·Chemistry : a European Journal·Angelo Perico, Alberto Ciferri
May 8, 2010·Chemical Society Reviews·Ramishetti SrinivasArabinda Chaudhuri
May 13, 2010·Chemical Society Reviews·Dana A UhlenheuerLuc Brunsveld
Apr 21, 2011·Angewandte Chemie·Ana C RodrigoDavid K Smith
May 18, 2011·Organic & Biomolecular Chemistry·Daniel J Welsh, David K Smith
Jul 26, 2011·Biochimica Et Biophysica Acta·James A Huntington
Sep 8, 2011·Angewandte Chemie·Siva Krishna Mohan NalluriBart Jan Ravoo
Jun 13, 2012·Angewandte Chemie·Anna Barnard, David K Smith
Sep 7, 2012·Angewandte Chemie·Carlo FastingRainer Haag
Nov 20, 2012·Organic & Biomolecular Chemistry·Katja Petkau-Milroy, Luc Brunsveld
Feb 15, 2013·Journal of the American Chemical Society·Stephen M BromfieldDavid K Smith
Apr 9, 2013·Organic & Biomolecular Chemistry·Daniel J WelshDavid K Smith
Apr 19, 2013·Chemical Communications : Chem Comm·Stephen M BromfieldDavid K Smith
Sep 11, 2013·Chemical Society Reviews·Stephen M BromfieldDavid K Smith
Oct 29, 2013·Journal of the American Chemical Society·Dongcui Li, Norman J Wagner
Jan 1, 2014·Chemical Science·Eric L DaneMark W Grinstaff
Feb 5, 2014·ACS Chemical Biology·Geronda L MontalvoWilliam F Degrado
Aug 11, 2015·Journal of the American Chemical Society·Stephen M Bromfield, David K Smith
Apr 21, 2014·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Ariane TschicheRainer Haag

❮ Previous
Next ❯

Citations

Jul 19, 2018·Chemistry : a European Journal·Vânia M P VieiraDavid K Smith
Oct 11, 2017·Chemical Communications : Chem Comm·Ana C RodrigoDavid K Smith
Jan 14, 2017·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Vania M P VieiraDavid K Smith
May 31, 2017·Chemical Communications : Chem Comm·Ana C RodrigoDavid K Smith
May 10, 2018·Chemistry : a European Journal·Wojciech DrożdżArtur R Stefankiewicz
Feb 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Domenico MarsonSabrina Pricl
Jun 11, 2020·ACS Applied Materials & Interfaces·Seon-Jin ChoiTimothy M Swager
Oct 23, 2018·Journal of the American Chemical Society·Yiwen DongLing Peng
Nov 5, 2019·ACS Chemical Biology·Benjamin Ourri, Laurent Vial

❮ Previous
Next ❯

Methods Mentioned

BETA
isothermal titration calorimetry
transmission electron microscopy

Software Mentioned

SAMul

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.