Designing ligands to bind proteins

Designing ligands to bind proteins.

The ability to design drugs (so-called 'rational drug design') has been one of the long-term objectives of chemistry for 50 years. It is an exceptionally difficult problem, and many of its parts lie outside the expertise of chemistry. The much more limited problem - how to design tight-binding ligands (rational ligand design) - would seem to be one that chemistry could solve, but has also prove...

Fishing out proteins that bind to titin

Another giant protein has been detected in cross-striated muscle cells. Given the name obscurin, it was discovered in a yeast two-hybrid screen in which the bait was a small region of titin that is localized near the Z-band. Obscurin is about 720 kD, similar in molecular weight to nebulin, but present at about one tenth the level (Young et al., 2001). Like titin, obscurin contains multiple immu...

DNA ligands that bind tightly and selectively to cellobiose.

Cell surface oligosaccharides have been shown to play essential biological roles in such diverse biological phenomena as cellular adhesion, molecular recognition, and inflammatory response. The development of high-affinity ligands capable of selectively recognizing a variety of small motifs in different oligosaccharides would be of significant interest as experimental and diagnostic tools. As a...

Peptide Ligands That Bind IgM Antibodies

How Proteins Bind Macrocycles

The potential utility of synthetic macrocycles (MCs) as drugs, particularly against low-druggability targets such as protein-protein interactions, has been widely discussed. There is little information, however, to guide the design of MCs for good target protein-binding activity or bioavailability. To address this knowledge gap, we analyze the binding modes of a representative set of MC-protein...