National Cancer Institute, Research Contracts Branch, PSAS, 6120 Executive Blvd, EPS/Room 638, Bethesda, MD 20892-7227

R -- PROFESSIONAL, ADMINISTRATIVE, AND MANAGEMENT SUPPORT SERVICES SOL RFQ-NCI-80108 DUE 042098 POC Cynthia Brown, Purchasing Agent, 301-402-4509, Todd Cole, Contract Officer The National Cancer Institute (NCI), proposes to procure scientific support services from Theodor Schulte, M.D., Research Molecular/Cell Biologist, to prepare a series of point mutants of hsp90, grp94, and related proteins, and to analyze these point mutants for their ability to bind the macrocyclic antibiotic radicicol and its derivatives. In addition, Dr. Schulte will develop biologic endpoints for in vivo, non-invasive determination of the biologic activity of these drugs as they are used in Phase I clinical trials. In 1994 NCI identified the benzoquinone ansamycin class of antibiotics, of which geldanamycin is one representative, as exerting their biologic activity by interacting directly with the hsp90 family of cellular chaperone proteins. NCI then utilized this drug to study the role of hsp90 in cancer growth. As part of these studies NCI has sought to determine the binding site of geldanamycin and its many dirivatives on hsp90, in order to better understand its mechanisim of action. These studies have involved production of hsp90 mutant proteins, their in vitro and in vivo translation, and analysis of their binding to geldanamycin derivatized to a solid support. Within the last year NCI identified a structurally novel natural product, radicicol, as another hsp90 antagonist, Dr. Schulte was the primary individual in this discovery process. The research conducted in the Medicine Branch, NCI is directed at studies of chaperone interaction with natural product inhibitory small molecules. Based on the research, the Contractor shall: 1) maintain a laboratory notebook which will meet all pertinent requirements of a research laboratory at the NCI, 2) archive and make available to other investigators in NCI/Medicine Branch any unique reagents (i.e., point mutants of hsp90 and grp94) which he/she creates during the period of the contract. In order to perform the required work, the individual shall have expertise in the analysis of the hsp90 family of chaperones and their interaction with the anti-cancer agents radicicol and geldanamycin. In addition, the individual shall have expertise in the novel methodologies to implement the techniques for these highly specialized studies. This notice is a combined synopsis/solcitation and NCI does not intend to issue a seperate solicitation, This solicitation, RFQ-NCI-80108, is set-aside for small business with a Standard Industrial Classification Code 8733. Dr. Theodor Schulte is the only source known to NCI that can meet these requirements. However, if any interested party believes it can meet the above specification, he/she may submit a statement of capabilities. Information furnished must be in writing and must contain material in sufficient detail to allow the NCI Researcher to determine if the party can perform the requirement. Capability statements must be received in the contracting office within 15 days after publication date of this notice. A determination by the Government not to compete this proposed contract based upon responses to this notice is solely withinthe discretion of the government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. (0092)

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