In 1996, Multiple Peptide Systems (MPS) was awarded a National Insitute of Drug Abuse contract (N01 DA-67053) to provide their associated researchers with highly purified opioid peptides and other centrally active neuropeptides. The contract in part includes the preparation and purification of labelled peptides having high specific activity at desired locations. Most of these compounds are not commercially available. The NIDA associated researchers are from private, academic and governmental research entities who obtain NIDA research grants in which they are given the opportunity to obtain the unique tritiated neuropeptides. In order to facilitate the production of these unique peptides, MPS has contracted the use of the National Tritium Labelling Facility at the Lawrence Berkeley National Laboratory. The comprehensive and unique laboratory facilities at the NTLF allow for higher quality compounds than those few products that are commercially available. With the specialized equipment and the knowledgeable employees, the facility is an excellent tool to permit labelling, purification and characterization of the tritium labelled compounds to be accomplished in a rapid, economical, and safe manner. Special precursors having either a labile halogen atom or a reactive double bond are prepared and purified at MPS. The precursor is dissolved in DMF. After addition of Palladium(II) oxide on charcoal as catalyst, the slurry is held in contact with tritium gas for 4 hours in the NTLF tritium reaction manifold. After recovery of the excess tritium and filtering of catalyst, the labelled peptide in solution is analyzed by liquid scintillation to check for activity. Afterwards, the newly tritiated compounds are purified to greater than 90% using preparative RP-HPLC with an in-line tritium beta counter detector. Tritium incorporation into the compound structure is checked by tritium NMR, which also gives an analysis tool for specific activity. The labelled peptides usually have specific activities ranging from 40 Ci/mmol to 55 Ci/mmol. The compounds are mainly used for research focusing on receptor characterization, metabolism studies (ADME: adsorption, distribution, metabolism and excretion) and identification of new active compounds (agonists or antagonists). Results from this research have direct application, as an example, in the development of unique analgesic drugs. User Details: Experiment Details: User Number: 1617 Tritiation City, State: San Diego, CA HPLC Funding Source: NIDA 3 N01 DA 67053 NMR Charge: $6250.91 4 days Program Income: $6247.54 8 compounds Secondary Users: Dr. Charles Chavkin University of Washington School of Medicine B00.of Pharmacology Health Sciences Building D425 Seattle, WA 98195 Dr. Paul L. Prather University of Arkansas Medical Sciences G154 4301 West Markham St. Little Rock, AR 72205 Dr. Robert P. Elde University of Minnesota Medical School 308 Harvard St. S.E. Minneapolis, MN 55455 Dr. Wolfgang Sadee School of Pharmacy University of California San Francisco, CA 94143 Dr. Marvin C. Gershengorn Cornell University Medical College 1300 York Avenue New York, NY 10021 Dr. Laura Sim-Selley Virginia Commonwealth University B00.of Pharmacology & Toxicology 112 East Clay St., McGuire Hall Rm 321 Richmond, VA 23298 Dr. Richard Kream New England Medical Center Tufts University School of Medicine B00.of Anesthesia 136 Harrison Ave., M&V 203 Boston, MA 02111 Dr. Eric Taylor Chiron Corporation 4560 Horton Street Emeryville, CA 94510
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