Volume 2 Issue 3, March 2006

Developing small-molecule inhibitors against protein-protein interaction targets is among the most difficult challenges in contemporary drug discovery. Recent developments in our understanding of this problem, and in the knowledge and tools available to address it, give cause for renewed hope, but substantial challenges remain.

Chemical biology continues to find its way into biomedical research in new and exciting ways. The recent American Society of Cell Biology meeting showed how this discipline is making an impact in areas such as cell biology.

Protein α-helices often terminate in recognizable helix-capping motifs. The origin of thermodynamic stability for one such motif is now well understood.

Enzymes that catalyze the formation of (S)-allantoin from the product of the urate oxidase reaction have been identified. This finding answers the longstanding question of how living organisms produce a single enantiomer of allantoin.

Bacteria are covered in sugars that facilitate the establishment of pathogenic or symbiotic relationships with other cells. Microarrays of carbohydrate-binding proteins now can provide quick snapshots of these sugar coats as they change during the bacterial life cycle and differ among bacterial strains.

Looked at from the outside of the cell, proteins are often hidden behind a forest of sugar chains. Using a sugar analog to introduce thiols onto the tips of the branches of this forest alters cell attachment and has unexpected consequences for cell differentiation.

Using single-molecule biophysical studies in an ion channel, the protonation state of engineered basic amino acids was measured in real time, making it possible to calculate the pK_as of the substituted residues and creating a unique, comprehensive dataset for theorists studying the effects of an electrostatic environment on integral membrane protein function.