Influence of length and flexibility of spacers on the binding affinity of divalent ligands

• Susanne Liese and
• Roland R. Netz

Beilstein J. Org. Chem. 2015, 11, 804–816, doi:10.3762/bjoc.11.90

• Susanne Liese Roland R. Netz Fachbereich für Physik, Freie Universität Berlin, 14195 Berlin, Germany 10.3762/bjoc.11.90 Abstract We present a quantitative model for the binding of divalent ligand–receptor systems. We study the influence of length and flexibility of the spacers on the overall

• value is derived. We find that a divalent ligand has the potential to bind more efficiently than its monovalent counterpart only, if the monovalent dissociation constant is lower than a critical value. This critical monovalent dissociation constant depends on the ligand-spacer length and flexibility as

• range as the size of a receptor binding pocket. Keywords: binding affinity; divalent ligand; effective concentration; multivalency; Introduction Multivalency is a common design principle in biological systems. The simultaneous binding of several, relatively weakly binding partners is a widely used

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• (Figure 10). Comparing the binding of a divalent ligand with its monomeric counterpart at decreasing ligand concentration showed a faster decay of binding for the monomeric ligand consistent with the speculation that, at high ligand concentration, the density was sufficiently high for the lectin to

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• analysis of ITC data. (A) Monovalent receptor (R)-ligand (L) interaction. (B) Multivalent interaction of a divalent receptor (RR) and a divalent ligand (LL). (C) 1:1 overall interaction of a divalent receptor (RR) and a divalent ligand (LL). (D) 2:1 interaction of a divalent receptor (RR) and a divalent

• ligand (LL). EM = effective molarity. See Supporting Information File 2 for details. Schematic drawing of the interactions of the divalent guest molecules 8 (A), 9 (B) and 10 (C) with complementary (right) and non-complementary (left) divalent CD strands. Schematic drawing of the interactions of the

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• . This indicates a change in the accessibility of the sugar ligands for receptor binding, with the Z-oligomer having a less accessible conformation. Following the same model as for the trivalent ligand, the divalent ligand has the opportunity to bind in a bivalent fashion in its E-form (Figure 3a) while

• - or Z-configurations, the divalent glycooligomers can only bind in a monovalent fashion explaining that no difference in binding affinity was observed upon photoswitching. Following this hypothesis, trivalent Azo-Gal(1,3,5)-5 would be reduced to an effective divalent ligand upon attachment to the SPR

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• their affinity for the target proteins, but can create solubility problems. Desilylation of 13 (TBAF, THF, Scheme 7) followed by in situ CuAAC with the pseudo-disaccharide 23 led to the divalent ligand 24, which was found to be fully soluble in water, at least up to millimolar concentrations. Compound

• still be further elongated, depending on the need of the project, thus enabling the preparation of long spacers with a well-defined number of monomeric units. The CuAAC of the three unit spacer 15 with a galactose ligand gave the divalent ligand 21 in good yield. After deprotection this compound was

• phenylene-ethynylene polymer core with ligands attached via flexible chains, and (b) a divalent ligand using phenylene-ethynylene as a rigid spacer connecting the ligands. Generic structure of spacers containing an even (n = 1, 3) and an odd (n = 2, 4) number of units. Synthetic strategy for rigid spacers

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• [36] and EPR spectroscopy [45]. Crystal structure analysis of a complex of WGA and four molecules of a divalent ligand containing two GlcNAc residues showed that each ligand bridged adjacent binding sites with a distance of approx. 13–14 Å between the anomeric oxygen atoms of the GlcNAc residues. This

• 2.8-fold increased inhibition potency of C6 over the best divalent ligand C4 indicates that C6 can reach only two WGA binding sites simultaneously due to its geometrical properties, which is fully in accordance with the structural investigations described below. Otherwise, a significantly stronger

• binding enhancement would have been expected comparable to the several-hundred-fold increase observed when moving from mono- to divalent ligand structures. Molecular modeling To provide a structure-based rationalization for the determined binding potencies of C2–C6, we performed molecular modeling studies