that my group is doing. And actually this is a very exciting time for chemists. We have sequenced the human genome, we know all the gene products of our genome and now of course a very important goal is to understand and to control the function of

each gene product. And that's why we chemists really can have an impact. For example we can make small molecules that can interfere with protein-protein interactions, we can make compounds that can interfere with transcription and translation of genetic processes such as small molecules that

bind to DNA or to RNA, or we can make small molecules that bind to enzyme inhibitors and knock out the functions of these enzymes. But think about it, I mean what does this mean? That means you want to make a molecule that really just interferes for example with the

function of a single enzyme. One enzyme out of 25,000 proteins together with all the DNA we have in the cell, the RNA, the membrane compartments and so on. So this is an enormous challenge of molecule recognition. And I claim and I think a lot of people will agree with me

that the typical current small organic molecule can actually not fulfill this task. So if you think about it, a typical bioactive organic molecule is a heterocyclic compound that has substituents on the periphery and the problem is it can adopt multiple conformations. And the

one conformation it binds to the one target and another conformation it binds to another target. So this promiscuity of conformation basically leads to this unselective binding. And the question is how can we solve this problem? That's what my group is really excited

about, this problem of molecule recognition. And if you think about solutions actually you can look to nature. Nature actually found ways to deal with this problem. You probably know that complicated natural products, they have very specific biological functions. They

sometimes really bind just to one particular target. And in order to understand how these natural products do that it's actually maybe important to have an example and to learn about how they interact with their respective targets. And I have here one slide that shows

the natural product, Galdana mycene, shown here. On the left it's already fairly complicated macrocyclic compound, multiple functional groups, multiple stereocenters, actually quite difficult to synthesize. And this compound actually binds selectively to the N-terminal

ATP binding site of the heat shock protein 90, Hsp90. And it does so by adopting this C shape. And in this C shape it binds to this very globular deep pocket. And when you look at the space filling model of this compound, how it binds to this pocket, it is basically like a globular shape with functional groups basically presented

on the surface. And that's what it comes down to. We have to basically find ways to make defined globular structures that have functional groups presented on the periphery in a very particular way. And nature does it by basically designing these complicated molecules in which

basically the scaffold in combination with all the functional groups and the stereocenters basically in a way code for a three-dimensional structure. And we don't, of course, we synthetic chemists, at least my group, we basically hesitate to make these complicated molecules

because the synthetic challenge is enormous and it's difficult to make maybe kilogram quantities of such a compound. So we were thinking about other ways how to basically make compounds that are globular, have a very defined shape, and because of this can then

bind very selectively to a target. Because you have to keep in mind that an active site is globular. It's typically a pocket. So you want to design globular molecules that are kind of rigid or have a defined shape and complement the shape of the functional group

representation of the active site. And if you think about organic chemistry, if you just have a benzene molecule or a heterocycle or a cyclohexane and you put substituents on it, these compounds are not rigid, they are not globular, they are basically flat disks more or less, and they have flexible arms. And if you want to make something that

is globular and has a defined shape, you typically need to fuse rings together, have bridging systems, have introduced stereocenters, other functional groups, and so on and so forth.