CORE--ORGANIC SYNTHESIS

有机合成设施（OSF）的主要目的是生产最高质量的 福克斯大通癌症中心（FCCC）的研究人员与同行评审的资金合成分子。有机小分子在许多研究领域中用作特异性试剂，包括酶活性或蛋白质结合的抑制剂。这些分子中的一些已用于开发针对在FCCC鉴定的靶蛋白的前药。天然底物的类似物已被用来探测酶的机制，研究蛋白质的功能，或测试特定的假设。该设施合成的分子不是从化学公司购买的，商业企业的定制合成要么无法获得，要么过于昂贵。研究人员要求的许多分子是新颖的，需要设计新的合成路线和纯化方案。对于以前已经合成的分子，该设施使用已公布的合成方案。然而，在超过50%的这些情况下，文献方案要么不按所述起作用，要么不产生足够纯的产物，并且设施必须设计新的合成或纯化方案。在上一个赠款期间（2000-2004年），完成了32种不同的化学合成，包括8种新化合物。合成的化合物在结构上非常多样，包括他莫昔芬代谢物、钆络合物、抗霉素类似物、氚标记的雌莫司汀、溴萘磺酸和自旋标记的腙。几种新型逆转录病毒整合酶抑制剂的合成（AIDS Res.复古。20：135-144，2004）证实了由OSF产生的质量科学。2000-2004年发表在同行评审期刊上的17篇文章（其中3篇由OSF工作人员合著）使用了在OSF中合成的化合物。使用OSF的同行评审资金的调查员人数从2000年的25人增加到2003年的34人（36%）。2003年的使用来自所有11个项目，98%的使用是由同行评审资金的研究人员使用的。这种用法包括合成、试剂纯化、化学分析和咨询。在核心赠款期间（2000-2004年），51名获得同行评审资金的调查员使用了开放社会基金的产品和服务。

The primary purpose of the Organic Synthesis Facility (OSF) is to produce the highest quality synthetic molecules for Fox Chase Cancer Center (FCCC) investigators with peer-reviewed funding. Small organic molecules are used in many areas of research as specific reagents including those that are inhibitors of enzyme activity or protein binding. Some of these molecules have been used in the development of prodrugs against target proteins identified at FCCC. Analogs of natural substrates have been used to probe enzyme mechanism, to investigate protein function, or to test specific hypotheses. The molecules synthesized by the Facility are not purchasable from chemical companies, and custom synthesis from commercial enterprises is either not available or prohibitively expensive. Many of the molecules requested by investigators are novel and require the design of new synthetic routes and purification schemes. For molecules that have been previously synthesized, the Facility uses the published synthetic protocol. However, in more than 50% of these cases, the literature protocol either does not work as described or does not yield a sufficiently pure product and the Facility has to design new syntheses or purification schemes. During the last grant period (2000-2004), 32 different chemical syntheses were completed including eight novel compounds. The compounds synthesized were very diverse in structure and included a tamoxifen metabolite, a gadolinium complex, an antimycin analog, tritium-labeled estramustine, bromo naphthalenesulfonic acid and spin-labeled hydrazone. The synthesis of several novel inhibitors of retroviral integrases (AIDS Res. Hum. Retro. 20:135-144, 2004) exemplifies the quality science generated by the OSF. Seventeen articles, three co-authored by OSF staff, published in peer-reviewed journals from 2000-2004 used compounds that were synthesized in the OSF. The number of investigators with peer-reviewed funding using the OSF has increased from 25 in 2000 to 34 in 2003 (36%). Usage in 2003 was from all 11 Programs and 98% of use was by investigators with peer-reviewed funding. This usage includes syntheses, purification of reagents, chemical analysis, and consultation. Fifty-one (51) investigators with peer-reviewed funding utilized products and services from the OSF during the Core Grant period (2000-2004).