Photoswitchable Multivalent Sugar Ligands:  Synthesis, Isomerization, and Lectin Binding Studies of Azobenzene−Glycopyranoside Derivatives

Oruganti, Srinivas; Mitra, N. K.; Surolia, Avadhesha; Jayaraman, Narayanaswamy

doi:10.1021/ja0173066

Cited by 64 publications

(39 citation statements)

References 33 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is seen, however, that the studies of the kinetics of the ligand-lectin interactions are much less known [18,19]. In our continuing studies on multivalent interactions [20][21][22][23], we undertook a detailed study of the kinetics of the bivalent vs monovalent sugar ligands during the lectin binding, by employing the SPR technique. The results were correlated with thermodynamic parameters, secured from the ITC measurements.…”

Section: Introductionmentioning

confidence: 99%

SPR and ITC determination of the kinetics and the thermodynamics of bivalent versus monovalent sugar ligand–lectin interactions

et al. 2007

Self Cite

View full text Add to dashboard Cite

A kinetic study of the interaction of bivalent and monovalent sugar ligands with a lectin was undertaken with the aid of surface plasmon resonance (SPR) method. The study involved a series of bivalent alpha-D-mannopyranoside containing sugar ligands, with systematic variation in the distance between the sugar ligands. The detailed kinetic studies showed that bivalent ligands underwent a faster association (k(on)) and a slower dissociation (k(off)) of the ligand-lectin complexes, in comparison to the monovalent ligand-lectin complexes. The kinetic constants were complemented further by assessing the thermodynamic parameters with the aid of isothermal titration calorimetry (ITC). The initiation of cross-linking of ligand-lectin interactions emerge from the early stages of the complexation. The dynamic light scattering (DLS) and the transmission electron microscopy (TEM) techniques allowed judging the sizes and morphologies of the complex in the solution and solid states, respectively.

show abstract

Section: Introductionmentioning

confidence: 99%

SPR and ITC determination of the kinetics and the thermodynamics of bivalent versus monovalent sugar ligand–lectin interactions

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Azobenzene and spiropyran are the most commonly used photoswitches in the design of molecules with photomodulated biological activity. [22][23][24][25][26][27][28] We have synthesized the glucoside 1 (Fig. 1) around the azobenzene photoswitch.…”

Section: Introductionmentioning

confidence: 99%

Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism

et al. 2015

View full text Add to dashboard Cite

Glycogen is a polymer of α-1,4- and α-1,6-linked glucose units that provides a readily available source of energy in living organisms. Glycogen synthase (GS) and glycogen phosphorylase (GP) are the two enzymes that control, respectively, the synthesis and degradation of this polysaccharide and constitute adequate pharmacological targets to modulate cellular glycogen levels, by means of inhibition of their catalytic activity. Here we report on the synthesis and biological evaluation of a selective inhibitor that consists of an azobenzene moiety glycosidically linked to the anomeric carbon of a glucose molecule. In the ground state, the more stable (E)-isomer of the azobenzene glucoside had a slight inhibitory effect on rat muscle GP (RMGP, IC50 = 4.9 mM) and Escherichia coli GS (EcGS, IC50 = 1.6 mM). After irradiation and subsequent conversion to the (Z)-form, the inhibitory potency of the azobenzene glucoside did not significantly change for RMGP (IC50 = 2.4 mM), while its effect on EcGS increased 50-fold (IC50 = 32 μM). Sucrose synthase 4 from potatoes, a glycosyltransferase that does not operate on glycogen, was only slightly inhibited by the (E)-isomer (IC50 = 0.73 mM). These findings could be rationalized on the basis of kinetic and computer-aided docking analysis, which indicated that both isomers of the azobenzene glucoside mimic the EcGS acceptor substrate and exert their inhibitory effect by binding to the glycogen subsite in the active center of the enzyme. The ability to selectively photoregulate the catalytic activity of key enzymes of glycogen metabolism may represent a new approach for the treatment of glycogen metabolism disorders.

show abstract

“…In order to gain such control over the binding affinity of glycooligomers towards specific lectins, a few studies have recently been dedicated to the construction of photoactive glycoligand incorporating a light-sensitive unit [12–15]. The possibility to photomodulate the complexation of a ligand could lead to a deeper understanding of the typically multivalent binding processes of carbohydrates to proteins, in addition to offer potential perspectives for the sensing and adhesion of bacteriological targets on various substrates.…”

Section: Introductionmentioning

confidence: 99%

Photoswitchable precision glycooligomers and their lectin binding

Ponader¹,

Igde²,

Wehle³

et al. 2014

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

SummaryThe synthesis of photoswitchable glycooligomers is presented by applying solid-phase polymer synthesis and functional building blocks. The obtained glycoligands are monodisperse and present azobenzene moieties as well as sugar ligands at defined positions within the oligomeric backbone and side chains, respectively. We show that the combination of molecular precision together with the photoswitchable properties of the azobenzene unit allows for the photosensitive control of glycoligand binding to protein receptors. These stimuli-sensitive glycoligands promote the understanding of multivalent binding and will be further developed as novel biosensors.

show abstract

Photoswitchable Multivalent Sugar Ligands: Synthesis, Isomerization, and Lectin Binding Studies of Azobenzene−Glycopyranoside Derivatives

Cited by 64 publications

References 33 publications

SPR and ITC determination of the kinetics and the thermodynamics of bivalent versus monovalent sugar ligand–lectin interactions

SPR and ITC determination of the kinetics and the thermodynamics of bivalent versus monovalent sugar ligand–lectin interactions

Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism

Photoswitchable precision glycooligomers and their lectin binding

Contact Info

Product

Resources

About