Biological Information Transfer Beyond the Genetic Code: The Sugar Code

Abstract

In the era of genetic engineering, cloning, and genome sequencing, the focus of research on the genetic code has received an even further accentuation in the public eye. When, however, aspiring to understand intra-and intercellular recognition processes comprehensively, the two biochemical dimensions established by nucleic acids and proteins are not sufficient to satisfactorily explain all molecular events in, e.g. cell adhesion or routing. To bridge this gap consideration of further code systems is essential. A third biochemical alphabet forming code words with an information storage capacity second to no other substance class in rather small units (words, sentences) is established by monosaccharides (letters). As hardware oligosaccharides surpass peptides by more than seven orders of magnitude in the theoretical ability to build isomers, then the total of conceivable hexamers is calculated. Beyond the sequence complexity application of nuclear magnetic resonance (NMR) spectroscopy and molecular modeling have been instrumental to discover that even small glycans can often reside in not only one but several distinct low-energy conformations (keys). Intriguingly, conformers can display notably different capacities to fit snugly into the binding site of nonhomologous receptors (locks). This process, experimentally verified for two classes of lectins, is termed "differential conformer selection." It adds potential for shifts of the conformer equilibrium to modulate ligand properties dynamically and reversibly to the wellknown changes of sequence (including anomeric positioning and linkage points) and of pattern of substitution, e.g. by sulfation. In the intimate interplay with sugar receptors (lectins, enzymes, and antibodies) the message of coding units of the sugar code is deciphered. This communication will trigger postbinding signaling and the intended biological response. Knowledge about the driving forces for the molecular rendezvous, that is, contributions of bidentate or cooperative hydrogen bonds, dispersion forces, stacking and solvent rearrangement, will enable the design * Reprinted with permission from Naturwissenschaften, Vol. 87 (2000), pp. 108-121. Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539 München, Germany, e-mail: gabius@tiph.vetmed.uni-muenchen

Patients with anaemia can shift from kidney to liver production of erythropoietin as shown by glycoform analysis

“…However, mammalian cells from different organs posttranslationally add a specific glycosylation signature to the produced glycoprotein [14].…”

Carbohydrate-based vaccines with a glycolipid adjuvant for breast cancer

“…The aberrations include loss or overexpression of certain glycan structures, persistence of truncated glycans, and emergence of novel glycans. Some of the aberrant glycans on malignant tissues were identified by immunohistochemical staining with lectins (2,3) or mAb or by MS (4,5). To date, numerous tumor-associated antigens expressed on cancer cells in the form of glycolipids or glycoproteins have been characterized and correlated to specific types of cancers (6,7).…”

Interaction Between Some Monosaccharides and Aspartic Acid in Dilute Aqueous Solutions

“…It is likely that an axial orientation of the OH group at C4 in the D-galactose molecule prevents formation of the associate between this monosaccharide and aspartic acid. The crucial role of spatial orientation of the OH group at C4 for the interactions between carbohydrates and molecular ligands as well as proteins has been stressed in a series of studies [9,12,[21][22][23]. D-Fructose is ketohexose (Fig.…”