PEPTIDE SYNTHESIS FACILITY

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The Contraception and Reproductive Health Branch of the NICHD supports a Chemical Synthesis Facility (CSF) that provides services central to the Branch's programs to develop safe and effective contraceptive agents. This Facility provides the Government with drugs, chemicals, chemical intermediates, steroids, and optically pure and/or resolved unnatural amino acids possessing >99% enantipmeric excess, which are either commercially unavailable or unduly expensive, for further contraceptive development by the Government. Specific Aims: The areas of chemical synthesis include: 1) orally active steroids, including;{ estrogens without 17 -ethynyla1cohol, orally active and long �acting androgens, e.g., testosterone bucyclate and 7cm, 11 p..dimethyl-19~nortestosterone bucyclate & undecanoate, orally active 7&a-methyI-19�nortestosterone (MENT) analogs, and progesterone receptor modulators (PRM),e.g., CDB-2914, 21-suhstituted analogs, e.g., CDB4124 (2nd generation) and novel derivatives (3rd generation) in combination of substititon at CllB-4-aryl and C17&a; 2) steroid haptens linked to bovine serum a1bumin as well as to histamine conjugates for the development of radioimmunoassay (RIA.); 3)radiolabeled compounds for RIA as tracers and for metabolism studies; 4) heterocyclic compounds including seconucleosides and hexahydroindenopyridine diastereomers ; and 5) alkylated iminosugars. The Contractor maintains and operate a Chemical Synthesis Facility (CSF) capable of (l) rapidly synthesizing laboratory scale quantities (1 to 5 grams) of specific chemical compounds required for initial contraceptive investigation in small animals, (2) synthesizing relatively larger quantities (up to <1 kg) of Some drugs for comprehensive antifertility testing by the Government, including preclinical and clinical studies under current Good Manufacturing Practices (cGMP); (3) synthesizing chemicals and/or chemical intermediates (up to < 1 kg) for use in other ongoing chemical. peptide and related contracts and other synthetic chemical contract programs; and (4) radiolabeled synthesis of compounds using 3H, I~C and 1251 for pharmacokinetics and metabolism studies.