Prof. Dr. Stephen J. Lippard
- Section Chemistry
- Location Cambridge, MA, USA, United States
- Election year 2004
Research
Professor Lippard’s laboratory discovered and named the first metallointercalators, platinum terpyridine complexes that insert between the DNA base pairs and unwind the duplex. This research was followed by extensive studies of the covalent interactions of cisplatin and related anticancer drugs with DNA. Included are the X-ray structural characterization of the major Pt-DNA adducts, 1,2-intrastrand cross-links, the discovery of high-mobility group and related proteins that bind specifically to these adducts, and elucidation of the details of the processing of Pt-DNA cross-links in living cells. A highlight of early work was the elucidation of the geometric and electronic structures of the platinum blues, first discovered over one hundred years ago.
Another major research area is the characterization of proteins that form the soluble methane monooxygenase (MMO) and related systems in bacteria. The Lippard group elucidated the structures of the hydroxylase enzymes from MMO, toluene monooxygenase, and phenol hydroxylase by X-ray crystallography in several oxidation states and with bound substrate analogs and product molecules. With the participation of several collaborators, many aspects of the molecular mechanism of dioxygen activation and alkane/arene hydroxylation were established. In parallel work, synthetic models of the carboxylate-bridged diiron center in the hydroxylase were prepared as both structural and functional mimics of the enzyme active sites.
These synthetic efforts also produced a beautiful series of polyiron complexes, including the molecular ferric wheel. In the area of metalloneurochemistry, his contributions include the synthesis of molecules that image zinc in neurons and provide the first real-time fluorescence images of both inducible and constitutive NO production in living cells.
Another major research area is the characterization of proteins that form the soluble methane monooxygenase (MMO) and related systems in bacteria. The Lippard group elucidated the structures of the hydroxylase enzymes from MMO, toluene monooxygenase, and phenol hydroxylase by X-ray crystallography in several oxidation states and with bound substrate analogs and product molecules. With the participation of several collaborators, many aspects of the molecular mechanism of dioxygen activation and alkane/arene hydroxylation were established. In parallel work, synthetic models of the carboxylate-bridged diiron center in the hydroxylase were prepared as both structural and functional mimics of the enzyme active sites.
These synthetic efforts also produced a beautiful series of polyiron complexes, including the molecular ferric wheel. In the area of metalloneurochemistry, his contributions include the synthesis of molecules that image zinc in neurons and provide the first real-time fluorescence images of both inducible and constitutive NO production in living cells.