There is no life without carbohydrates on our planet. Full stop.
Not only do carbohydrates and glycoconjugates (glycolipids, glycoproteins, various) represent the initial storage form of the sun’s energy but, moreover, they determine survival as well as livelihood of all known species on our planet due to their many vital roles in living systems. There is probably no correctly working protein without glycosylation sites that influence its folding process, life span and function and there would be no working cell without subtle carbohydrate based “information beacons” on its surface. Consequently, due to the carbohydrates’ manifold roles in life as we know it, a plethora of highly specialised enzymes and enzyme cascades is operative to sustain biosynthesis, maintenance and catabolism of glyco-compounds in nature.
Understanding and modulating carbohydrate processing enzymes has been one of the major tasks in order to address disease development at molecular level. Glycosyl transferases, -phosphorylases as well as glycoside hydrolases (glycosidases) are involved in protein functionalisation, the building up of vital glycolipids and many other processes in healthy organisms.
Subtle dys-balances in enzyme activities or compromised individual enzymes may lead to severe failures in metabolic processes and feedback cycles and thus to disease and premature death of affected organisms.
Numerous efforts and attempts to learn about selectivities as well as conformational requirements and pathways of glycosidases have provided a good understanding of principle facts concerning this large family of enzymes. Apart from general kinetic considerations, various kinds of inhibitors as well as advancements in XRD have considerably contributed to contemporary knowledge.
Amongst the various types of inhibitors, low molecular weight iminosugars, carbasugars and certain types of highly functionalised, water-soluble bicyclic alkaloids have frequently been exploited. Some of these compounds were also found useful medications or promising leads for several diseases including diabetes type II, adipositas, certain viral infections, lysosomal storage diseases, some forms of cancer and others.
Most of these compounds contain a basic nitrogen either replacing the ring nitrogen of a “normal” sugar, C-1, or the anomeric oxygen. Thus, imino sugars (1), isoimino sugars (2) and amine substituted carbasugars (3) may be distinguished as the main scaffolds.
After a long and exciting period in the area of imino sugars, we are currently exploring isoimino sugars as well as selected carba sugars both of which allow for structural modifications unavailable with imino sugars.
In particular, the influence of various substituents on ring conformations and, consequently, selectivities of recognition/binding are currently investigated.