National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Natcher Builiding, 45 Center Drive MSC 6600, Room 6AN32, Bethesda, Maryland 20892-6600

66 -- INTRACAVITY FREQUENCY-DOUBLED ARGON ION LASER SOL NIH-NIDDK-95-8 DUE 041895 POC Katrina James, Contract Specialist, 301/594-7730. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) intends to contract on a sole source basis with Coherent Laser Group, Santa Clara, CA for a Innova 300 FReD (Intracavity Frequency-Doubled Ion Laser). The required wavelengths must be those that can excite fluorescence of tryptophan (spectral region 250-300nm and those that can be used in the required circular dichroism and optical rotatory dispersion measurements (220-235 nm). The purpose of this is to understand the dynamics and structural changes that occur during the early events in protein (un)folding; and develop spectroscopic techniques for studying protein (un)folding kinetics on the microsecond to nanosecond time scales. The NIDDK is engaged in the investigation of protein (un)folding kinetics on faster times scales than are possible by commercially available stopped-flow methods. Two methods are currently being developed to initiate fast protein folding from the denatured state. One is to use a nanosecond laser pulse to initiate protein folding by photochemistry, and the second is to use a nanosecond laser pulse to rapidly heat the water solvent to study the unfolding process. Both of these methods require observations on very small sample volumes (less than 1/10th microliter). To probe protein folding on such small volume with sufficient signal-to-noise requires a source of light that is extremely stable (better than 1% long-term power stability in the far UV), intense and can be focussed to a few microns in order to measure an area (in the laser temperature-jump experiments) of uniform temperature. Such a source must therefore be a laser. In addition to stability and intensity, the laser must satisfy two other requirements. It must have low peak power and appropriate ultrviolet wavelengths for the excitation of fluorescence and the measurement of circular dichroism or optical rotatory dispersion. The low peak power is necessary to prevent irreversible photodamage of the protein; pulsed lasers are therefore not to be considered as a candidate for the laser source required for this work. The required wavelengths must be those that can excite fluorescence of tryptophan (spectral region 250-300 nm) and those that can be used in the required circular dichroism and optical rotatory dispersion measurements (220-235 nm). The fluorescence signal gives information on formation of a compact structure from the random coil, denatured state, while the circular dichroism and optical rotatory dispersion give information on the formation of secondary structure, such as alpha helix and beta sheet. Monitoring the folding process by fluorescence and optical activity measurements requires a particularly stable laser because of the inherently low signal levels in these experiments. The requested intracavity frequency-doubled argon ion laser will provide a very stable UV light source necessary for acquiring kinetic data with sufficient signal-to-noise. This improved signal-to-noise will enable us to obtain new information about the dynamics of protein folding processes. Purchasing of this laser system that provides tunable UV wavelengths, high continuous wave output powers, and long-term power stability is essential in order to be able to optimally carry out optical spectroscopic kinetic studies of protein folding processes. The NIH believes that the proposed contractor is the only source available as it is uniquely qualified to provide the subject laser. This is not a formal solicitation. However, concerns that response should furnish detailed data concerning their capabilities demonstrating the offeror ability to provide that equipment needed. This notice may represent the only official notice of such a solicitation. (See Notice 22). (0059)

Loren Data Corp. http://www.ld.com (SYN# 0277 19950301\66-0017.SOL)