DNA-programmed spatial screening of carbohydrate–lectin interactions

Scheibe, Christian; Bujotzek, Alexander; Dernedde, Jens; Weber, Marcus; Seitz, Oliver

doi:10.1039/c0sc00565g

Cited by 86 publications

(69 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In our approach, we were able to screen 52 different multivalent assemblies over a valency range of 1 to 45 ligands to find an optimal one that improved the potency of each RGD ligand by about 2 orders of magnitude. We believe this strategy, in addition to a recently published γ-Cys-version 22 , could greatly aid the exploration of multivalent assemblies especially if incorporated with other strategies to manipulate the three-dimensional architecture of DNA 34 .…”

Section: Discussionmentioning

confidence: 99%

“…Substituting one or more of the regular aeg PNA residues in the synthesis with a monomer that contains an attachment point allows cyclic-RGD-containing ligands, which are antagonists of α v β 3 integrins, to be placed anywhere along the PNA. For this step, we used L-lysine γ-substituted peptide nucleic acid ( L Kγ-PNA), whose lysine sidechain is available for conjugation and does not interfere with nucleic acid binding 20–22 . Finally, using nucleic acid-driven assembly of ligand-conjugated L Kγ-PNA oligomers and ssDNA containing varying numbers of repeating complementary sequences, we can rapidly form libraries of multivalent molecules with precise numbers and densities of ligands (Figs.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds

et al. 2012

View full text Add to dashboard Cite

Multivalent effects dictate the binding affinity of multiple ligands on one molecular entity to receptors. Integrins are receptors that mediate cell attachment through multivalent binding to peptide sequences within the extracellular matrix, and overexpression promotes the metastasis of some cancers. Multivalent display of integrin antagonists enhances their efficacy, but current scaffolds have limited ranges and precision for the display of ligands. Here we present an approach to study multivalent effects across wide ranges of ligand number, density, and three-dimensional arrangement. Using L-lysine γ-substituted peptide nucleic acids, the multivalent effects of an integrin antagonist were examined over a range of 1 to 45 ligands. The optimal construct improves the inhibitory activity of the antagonist by two orders of magnitude against the binding of melanoma cells to the extracellular matrix in both in vitro and in vivo models.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds

et al. 2012

View full text Add to dashboard Cite

show abstract

“…16 Inspired by our research, Seitz and co-workers demonstrated that oligosaccharide-displayed peptide nucleic acid (PNA) ODN complexes were useful for the spatial screening of oligosaccharidelectin interactions. 17,18 They also demonstrated that bivalent peptide-displayed duplexes with regular intervals as molecular rulers effectively bound to tandem SH2 domain of Syk kinase. 19 Moreover, Montesarchio and co-workers reported antiviral activity against HIV-1 of glycoconjugated DNA quadruplex.…”

Section: ¹1mentioning

confidence: 99%

Construction of Functional Biomaterials by Biomolecular Self-Assembly

Matsuura

2017

Bulletin of the Chemical Society of Japan

View full text Add to dashboard Cite

This account discusses construction strategies for various functional biomaterials based on the designed self-assembly of biomolecules. Novel glycoclusters with regular intervals were developed by self-assembly of carbohydrate-conjugated oligodeoxyribonucleotides (ODNs) with the half-sliding complementary ODNs. Complexes of carbohydrate-modified DNA and lectin afforded a new regulation system for gene expression. DNA three-way junctions bearing self-complementary stickyends were self-assembled into nanometer-to-micrometer-sized spherical structures depending on the concentration. The threeway component design was extended to the design of an artificial trigonal peptide conjugate. The trigonal peptide conjugates bearing ¢-sheet-forming peptides or glutathione selfassembled into nano-sized spherical assemblies. Self-assembly of ¢-annulus peptide derived from tomato bushy stunt virus afforded artificial viral capsids, which can encapsulate and be modified with various molecules.

show abstract

“…Our group and others have used this strategy with a typical gain in binding affinity ranging from 10-to 1000-fold as a result of the synergic interaction of displayed ligands. [32,35,[40][41][42][43][44][45][46][47][48][49][50] Pioneering efforts in the area were reported by Kobayashi and coworkers with the oligomerization of a half slide complementary DNA fragment derivatized with galactose to generate periodic glycocluster. [51,52] Neri and coworkers were the first to use complementary sequences within the tag to pair small molecule fragments using self-hybridization.…”

Section: Introductionmentioning

confidence: 99%

Nucleic Acid-programmed Assemblies: Translating Instruction into Function in Chemical Biology

Winssinger¹

2013

Chimia

View full text Add to dashboard Cite

The predictability of nucleic acid hybridization offers an attractive platform to program the assembly of tagged ligands or reactants. Hybridization can be used to display multiple ligands in order to gain affinity and/ or selectivity through the cooperative interaction of each ligand. Additionally, hybridization of tagged reagents increases their effective concentration and accelerates reactions. In both cases, an oligonucleotide directs an assembly to yield a functional output in the form of enhanced binding, inhibition, or reaction; for example, a reaction can be used to unmask a fluorophore or a bioactive molecule. This review provides an account of our research in this area as well as future directions.

show abstract

DNA-programmed spatial screening of carbohydrate–lectin interactions

Cited by 86 publications

References 33 publications

Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds

Programmable multivalent display of receptor ligands using peptide nucleic acid nanoscaffolds

Construction of Functional Biomaterials by Biomolecular Self-Assembly

Nucleic Acid-programmed Assemblies: Translating Instruction into Function in Chemical Biology

Contact Info

Product

Resources

About