This proposal seeks partial funding (400,000 dollars) through the NIH Shared Instrumentation Program for the purchase of a 500 Mhz NMR spectrometer. This instrument is requested to replace our 1994 model Bruker 200 Mhz spectrometer which is obsolete and no longer capable of fulfilling our research needs. The total cost of the proposed high field spectrometer with accessories is about 700,000 dollars. The University of Texas M.D. Anderson Cancer Center (UTMDACC) has committed funds for the balance of the acquisition costs as well as for housing the instrument and supporting its operating expenses for a period of two years. Thereafter, the operation and maintenance of the instrument will be funded through a charge-back mechanism to user research grants with partial support also being derived from our institutional Cancer Center Support Grant. Currently, 10 NIH funded research projects at the UTMDACC and one from the UTHSC require NMR spectrometry for structural studies. Many of these deal with the development of a new cancer therapeutics where NMR is used extensively to characterize chemical reaction intermediates and products, to investigate the structure of drug metabolites, and to study drug interactions with target sites. The Principal Investigators of these projects are affiliated with six different clinical departments and three basic science departments and would account for approximately 80 percent use of the NMR. An additional group of 7 Principal Investigators, each with peer reviewed grants, also require NMR for their research. As already noted, the only on-site NMR spectrometer available to meet this need is a 20OMhz Bruker. This instrument is now 13 years old, is failing rapidly, and has a short operational life expectancy. In addition, the comparatively low field strength and limited analytical capabilities of the instrument are unable to provide the sophisticated structural information necessary to fulfill the present and rapidly emerging requirements of the funded research projects. A new 500-Mhz spectrometer should redress this deficiency and allow the UTMDACC to maintain a competitive edge in the development of new drug therapies to reduce the burden of cancer. The instrument will also be used to train graduate students and postdoctoral fellows in the applications of modern high-field NMR technology in medicinal chemistry, pharmacology, and medicine, and would allow the institution to recruit additional faculty who require this type of instrumentation.
