Paul B. Hopkins
Bio-organic ChemistryBioorganic chemistry is the chemistry of life. The Hopkins group brings the experimental techniques and theories of modern organic chemistry to bear on problems of structure and reactivity involving Nature's molecules. Current projects probe the secrets of Nature's most magnificent molecules, the proteins and nucleic acids, as well as her more modest, but no less seductive, smaller molecules. The tools of today allow the organic chemist to tackle problems which only a decade ago seemed insurmountable. As a result, opportunities open to those trained in organic chemistry include myriad fascinating challenges both traditional and decidedly non-traditional.
Double helical DNA is a molecule of great interest to the Hopkins group. By combining the powerful tools of organic synthesis with those of solid phase biopolymer synthesis, Hopkins's students are making nucleic acids which contain unnatural residues. In one project, a probe for molecular motion is built into the heart of DNA; the spectroscopic red flag that this probe waves tells scientists about the physical gyrations this macromolecule undergoes. An unanticipated benefit of this work has been the discovery that DNA structures can be detected by their "dynamic signatures." Syntheses of new nucleic acid motion probes and their incorporation are underway and promise to yield exciting and unexpected results.
Nature's system for storing and reproducing the genetic material is beautiful, but not foolproof. A class of agents known as bifunctional alkylating agents thwart DNA's grand design by covalently linking the intertwined threads of the duplex to one another: so joined, the strands cannot separate to fulfill their appointed tasks.
Hopkins's students have embarked on a general program to define the chemistry of reactions of bifunctional alkylating agents with duplex DNA. Their results have already pinpointed the precise sites at which many such lesions are formed by highly toxic, naturally and unnaturally derived substances. The techniques they have pioneered hold great promise for unraveling the mechanisms by which these sites in DNA are cross-linked.
Students in this group are exposed to a wide variety of experimental and theoretical techniques, and learn to think about problems in an array of disciplines. Electron spin resonance, gel electrophoresis, and automated solid phase synthesis are as likely to be used as the thin layer chromatography plate and infrared spectrophotometer of classical organic chemistry. It is no coincidence that so many organic chemists are thinking about biological problems: it is a field of great excitement.