4 research outputs found
Mechanistic Studies of the Zirconium−Triisopropanolamine-Catalyzed Enantioselective Addition of Azide to Cyclohexene Oxide â€
Discovery of a crystalline sulforaphane analog with good solid-state stability and engagement of the Nrf2 pathway in vitro and in vivo
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>) Discovered through X‑ray Fragment Screening
Elevated levels of
human lipoprotein-associated phospholipase A2
(Lp-PLA<sub>2</sub>) are associated with cardiovascular disease and
dementia. A fragment screen was conducted against Lp-PLA<sub>2</sub> in order to identify novel inhibitors. Multiple fragment hits were
observed in different regions of the active site, including some hits
that bound in a pocket created by movement of a protein side chain
(approximately 13 Ã… from the catalytic residue Ser273). Using
structure guided design, we optimized a fragment that bound in this
pocket to generate a novel low nanomolar chemotype, which did not
interact with the catalytic residues
Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA<sub>2</sub>) Discovered through X‑ray Fragment Screening
Elevated levels of
human lipoprotein-associated phospholipase A2
(Lp-PLA<sub>2</sub>) are associated with cardiovascular disease and
dementia. A fragment screen was conducted against Lp-PLA<sub>2</sub> in order to identify novel inhibitors. Multiple fragment hits were
observed in different regions of the active site, including some hits
that bound in a pocket created by movement of a protein side chain
(approximately 13 Ã… from the catalytic residue Ser273). Using
structure guided design, we optimized a fragment that bound in this
pocket to generate a novel low nanomolar chemotype, which did not
interact with the catalytic residues