Automated Flow Peptide Synthesis Enables Engineering of Proteins with Stabilized Transient Binding Pockets.

Engineering at the amino acid level is key to enhancing the properties of existing proteins in a desired manner. So far, protein engineering has been dominated by genetic approaches, which have been extremely powerful but only allow for minimal variations beyond the canonical amino acids. Chemical peptide synthesis allows the unrestricted incorporation of a vast set of unnatural amino acids with much broader functionalities, including the incorporation of post-translational modifications or labels.

Binding pocket stabilization by high-throughput screening of yeast display libraries.

Protein dynamics have a great influence on the binding pockets of some therapeutic targets. Flexible protein binding sites can result in transient binding pocket formation which might have a negative impact on drug screening efforts. Here, we describe a protein engineering strategy with FK506-binding protein 51 (FKBP51) as a model protein, which is a promising target for stress-related disorders.

Med Chem Remote: The Frontiers in Medicinal Chemistry 2021.

Digital, but delicious! The Frontiers in Medicinal Chemistry 2021 meeting, originally intended to take place in Darmstadt, carried on as an online event from March 8-10 this year. Even with pandemic restrictions, the event co-presented by the Medicinal Chemistry Division of the German Chemical Society (GDCh), the German Pharmaceutical Society (DPhG), and the Swiss Chemical Society (SCS) proved to be a success, showcasing excellent speakers and facilitating participant interaction in an ingenious virtual setting. Over 350 participants from more than 10 countries gathered to discuss the latest trends and directions in medicinal chemistry, with sessions on molecular glues, covalent fragments, transient binding pockets and more.

Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity.

Subtype selectivity represents a challenge in many drug discovery campaigns. A typical example is the FK506 binding protein 51 (FKBP51), which has emerged as an attractive drug target. The most advanced FKBP51 ligands of the SAFit class are highly selective vs.