Lectin ligands: New insights into their conformations and their dynamic behavior and the discovery of conformer selection by lectins

The mysteries of the functions of complex glycoconjugates have enthralled scientists over decades. Theoretical considerations have ascribed an enormous capacity to store information to oligosaccharides, In the interplay with lectins sugar-code words of complex carbohydrate structures can be deciphered. To capitalize on knowledge about this type of molecular recognition for rational marker/drug design, the intimate details of the recognition process must be delineated, To this aim the required approach is garnered from several fields, profiting from advances primarily in X-ray crystallography, nuclear magnetic resonance spectroscopy and computational calculations encompassing molecular mechanics, molecular dynamics and homology modeling. Collectively considered, the results force us to jettison the preconception of a rigid ligand structure. On the contrary, a carbohydrate ligand may move rather freely between two or even more low-energy positions, affording the basis for conformer selection by a lectin. By an exemplary illustration of the interdisciplinary approach including up-to-date refinements in carbohydrate modeling it is underscored why this combination is considered to show promise of fostering innovative strategies in rational marker/drug design

Structure evolution in amylopectin/ethylene glycol mixtures by H-bond formation and phase separation studied with dielectric relaxation spectroscopy

The interaction between amylopectin, a starch polysaccharide, and ethylene glycol (EG) was investigated using broad-band dielectric relaxation spectroscopy. Water-free amylopectin (AP) was mixed with 21 wt % ethylene glycol. This resulted in a continuous ethylene glycol phase, as well as a molecularly mixed AP/EG fraction. After storage at room temperature or annealing, the mixture shows dynamic properties typical of a polymer with weak intermolecular interactions, suggesting that EG binds preferentially to AP and forms intrachain H-bridges leading to increased chain stiffness and thus an increased glass transition temperature. This structure evolution is accompanied by a sharp reduction in the size of the ethylene glycol droplets to a few nanometers, as revealed by pronounced confinement effects in the alpha -relaxation of the dispersed EG.status: publishe

Proteomic and functional characterization of endogenous adiponectin purified from fetal bovine serum

Adiponectin is a plasma protein exclusively secreted from fat tissue. Many recent pharmacological studies suggest that recombinant adiponectin has multiple therapeutic potentials for obesity-related metabolic disorders, including type 2 diabetes, dyslipidemia, insulin resistance and atherosclerosis. However, the physiological relevance of these findings remains to be further established. In the present study, we have purified endogenous adiponectin from fetal bovine serum and characterized its post-translational modifications and physiological functions in animal models. Endogenous bovine serum adiponectin consists predominantly of full-length proteins that form multiple oligomeric complexes, including trimers, hexamers and higher molecular species. Two-dimensional gel electrophoresis revealed that bovine serum adiponectin exists as multiple post-translationally modified isoforms with distinct molecular weight and isolectric point. Further analysis using mass spectrometry and Edman degradation sequencing demonstrated that five conserved lysine residues (Lys 28, 60, 63, 72 and 96) within the collagenous domain of bovine adiponectin are hydroxylated and glycosylated by a glucosylα(1-2)galactosyl group. Injection of endogenous bovine adiponectin into C57 mice potently decreased circulating glucose levels and enhanced lipid clearance after a high fat meal. Chronic administration of this protein for a period of two weeks significantly increased insulin sensitivity and glucose tolerance, and depleted hepatic lipid accumulation in high-fat fed mice. These results provide direct evidence that endogenous bovine adiponectin is a physiological hormone that can regulate lipid and glucose metabolism.link_to_subscribed_fulltex