According to the study it is showing that the synthesis of a potential immunosuppressive agent; by modification of a naturally occurring compound. In this endeavour, the researchers have employed a masking trick to “hide” a reactive species inside the target molecule. Particularly fascinating are the so-called Natural products.
These are substances producing by living organisms; for the most diverse functions: defense, sensing, signaling, among others. For example, a plant which is threatening by a certain parasite might develop; through evolution over a period of many thousands of years, the ability to produce certain classes of chemicals that can either kill or at least repel the said parasite.
Natural products often possess very sophisticated chemical structure; and are species-specific meaning, they are producing only by a selecting species of organisms. Immunosuppressive drugs are widely using in the treatment of allograft repulsions and autoimmune associated diseases. Although a range of such drugs have been developed and are used clinically, almost all of them carry severe side effects and limitations.
Potential immunosuppressive agent
The search for new immunosuppressants with a distinct mode of action is therefore an urgent need to improve the safety and efficiency of immunosuppressive therapy. Several research groups have attempted the laboratory synthesis of the FR molecules in the years that followed with mitigated sucess. novel chemical reaction that allows the preparation of such macrocyclic structures in high efficiency and from simple precursors.
But the FR252921, FR252922, and FR256523 are a family of potent macrocyclic polyene immuno suppressive agents with a novel mode of action. However, the lack of an efficient and flexible synthesis has hindered further biological studies, mostly due to the fact that the natural products appear to be kinetic isomers regarding the triene moiety.
But the study simply hide the double bonds in a ‘secured’ form; so that they can be revealing at a later stage. Furthermore, the compounds we prepare in the lab; are indistinguishable from those isolating from Pseudomonas fluorescens. As the researchers are now able to reproduce these complex structures in the lab; they are in a position to introduce non-natural variations and modifications of those structures.
They already found an analogue that is almost 100 times more potent; than the compounds produced by Nature. The joint collaboration between University of Vienna and CeMM has resulted in true synergies. This in turn enables ready access to a range of unnatural analogues; among which several compounds showed inhibition of T-lymphocyte proliferation; at levels equal or superior to those of the natural products themselves.