OPERATION AND MAINTENANCE OF A PEPTIDE FACILITY

避孕和生殖健康处支持一个化学合成设施，该设施为该处开发安全有效避孕药物的方案提供核心服务。该设施向政府提供药品、化学品、化学中间体、类固醇以及具有超过99%对映体过量的光学纯和/或已分解的非天然氨基酸，供政府进一步开发避孕药具之用，这些药品要么在商业上无法获得，要么价格过高。化学合成领域包括：1)口服活性类固醇，包括；不含17 -乙基醇的雌激素，口服活性和长效雄激素，如丁环睾酮和7cm， 11p。丁环酸二甲基-19~去甲睾酮和十一酸二甲基-19~去甲睾酮（MENT）类似物，孕激素受体调节剂（PRM）等。CDB-2914, 21取代类似物，例如CDB4124（第二代）和cllb -4-芳基和C17&a取代组合的新衍生物（第三代）；2)结合牛血清白蛋白和组胺偶联物的类固醇半抗原，用于放射免疫测定（RIA）的发展；3)放射性标记化合物，用于RIA示踪剂和代谢研究；4)杂环化合物，包括二核苷和六氢独立吡啶非对映体；5)烷基化亚糖。承包商维护和操作一个化学合成设施（CSF），能够(1)快速合成实验室规模数量（1至5克）的特定化合物，用于小动物的初步避孕调查；(2)合成相对较大数量（高达<1公斤）的一些药物，用于政府的全面抗生育试验，包括根据现行良好生产规范（cGMP）进行的临床前和临床研究；(3)用于其他正在进行的化学品的合成化学品和/或化学中间体（不超过1公斤）。多肽及相关合同及其他合成化学品合同项目；(4)利用3H、I~C和1251进行放射性标记合成化合物的药代动力学和代谢研究。

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. .