Chemical Biology of the Sugar Code

Abstract

A high-density coding system is essential to allow cells to communicate efficiently and swiftly through complex surface interactions. All the structural requirements for forming a wide array of signals with a system of minimal size are met by oligomers of carbohydrates. These molecules surpass amino acids and nucleotides by far in information-storing capacity and serve as ligands in biorecognition processes for the transfer of information. The results of work aiming to reveal the intricate ways in which oligosaccharide determinants of cellular glycoconjugates interact with tissue lectins and thereby trigger multifarious cellular responses (e.g. in adhesion or growth regulation) are teaching amazing lessons about the range of finely tuned activities involved. The ability of enzymes to generate an enormous diversity of biochemical signals is matched by receptor proteins (lectins), which are equally elaborate. The multiformity of lectins ensures accurate signal decoding and transmission. The exquisite refinement of both sides of the protein-carbohydrate recognition system turns the structural complexity of glycans--a demanding but essentially mastered problem for analytical chemistry--into a biochemical virtue. The emerging medical importance of protein-carbohydrate recognition, for example in combating infection and the spread of tumors or in targeting drugs, also explains why this interaction system is no longer below industrial radarscopes. Our review sketches the concept of the sugar code, with a solid description of the historical background. We also place emphasis on a distinctive feature of the code, that is, the potential of a carbohydrate ligand to adopt various defined shapes, each with its own particular ligand properties (differential conformer selection). Proper consideration of the structure and shape of the ligand enables us to envision the chemical design of potent binding partners for a target (in lectin-mediated drug delivery) or ways to block lectins of medical importance (in infection, tumor spread, or inflammation).

Photoderivatized Polymer Thin Films at Quartz Crystal Microbalance Surfaces: Sensors for Carbohydrate−Protein Interactions

“…Flash column chromatography was performed on silica gel 60 (SDS 0.040-0.063 mm). 1 H and 13 C spectra were recorded with a DMX 500 instrument (Bruker) at 298 K in CDCl 3 using the residual signal from CHCl 3 ( 1 H NMR, δ = 7.25 ppm; 13 C NMR, δ = 77.0 ppm) as an internal standard. Quartz crystal microbalance experiments were performed using an Attana 100 instrument (Attana).…”

“…Purification of the residue by flash column chromatography (hexane/ethyl acetate 6:1) afforded compound 3 in 40% yield (0.49 g). 1 H NMR (500 MHz, CDCl 3 ) δ 3.03 (4H, t, J = 6.5 Hz, CH 2 -S), 4.62 (4H, t, J = 6.5 Hz, CH 2 -OCO); 13 …”

“…[10][11][12][13][14] Interactions between cellular glycans and proteins have been found to be of special importance in many biological processes, being involved in cell-cell interactions, cell communication, cell proliferation, and cell death. This emerging significance prompts for new means to analytically study these interactions.…”

Assessing the inhibitory potency of galectin ligands identified from combinatorial (glyco)peptide libraries using surface plasmon resonance spectroscopy

“…The emerging functionality of glycans as sugar-encoded signals, translated into cellular responses by endogenous lectins, entails a medical perspective [1]. Explicitly, undesired interactions in vivo mediated by lectin-glycan recognition become a target for inhibitor development.…”

“…Explicitly, undesired interactions in vivo mediated by lectin-glycan recognition become a target for inhibitor development. Such attributes apply to the lectin family of galectins [1,2]. Due to their involvement in intercellular interactions in processes such as angiogenesis and tumor invasion/spread, as well as in intracellular recognition processes encompassing antiapoptotic and promalignant activities via binding to distinct protein targets such as Bcl-2 and oncogenic H-ras, especially human galectins 1 and 3 (h-Gal-1 1 and h-Gal-3, respectively) are attractive models for innovative drug design.…”