Perry M J, Higgs G A
Celltech Therapeutics Ltd, Berkshire, UK.
Curr Opin Chem Biol. 1998 Aug;2(4):472-81. doi: 10.1016/s1367-5931(98)80123-3.
The application of molecular cloning has revealed the phenomenal diversity and complexity of the phosphodiesterase isoenzyme family. Thus, more than 30 human phosphodiesterases are now known; all are apparently necessary for the seemingly simple task of hydrolysing the 3'-ester bond of either cyclic adenosine monophosphate or cyclic guanosine monophosphate. The availability of phosphodiesterase isoenzymes as pure recombinant proteins has greatly facilitated the identification of potent, selective inhibitors. The potential of these inhibitors to therapeutically exploit the molecular diversity of the phosphodiesterases has progressed significantly. A number of drugs are in clinical trials for asthma, and Viagra has become the first selective phosphodiesterase inhibitor to be approved by the US Food and Drug Administration.
分子克隆技术的应用揭示了磷酸二酯酶同工酶家族惊人的多样性和复杂性。因此，目前已知有30多种人类磷酸二酯酶；对于水解环磷酸腺苷或环磷酸鸟苷的3'-酯键这一看似简单的任务而言，所有这些酶显然都是必需的。磷酸二酯酶同工酶作为纯重组蛋白的可得性极大地促进了强效、选择性抑制剂的鉴定。这些抑制剂在治疗上利用磷酸二酯酶分子多样性的潜力已取得显著进展。一些药物正在进行哮喘的临床试验，而伟哥已成为首个获得美国食品药品监督管理局批准的选择性磷酸二酯酶抑制剂。
