TISSUE SPECIFIC INHIBITORS OF PHOSPHODIESTERASE

该计划的一个目标是制备不可逆的抑制剂， cAMP特异性和钙调素敏感性形式的环核苷酸 磷酸二酯酶 亲和探针将用于确定部分的 钙调素敏感蛋白水解位点的氨基酸组成 磷酸二酯酶 不可逆抑制与 完整猪冠状动脉和细胞内cAMP水平 和环GMP将被确定，以确定哪种形式的 酶主要负责每个核苷酸的调节。 在本计划的第二个方面，我们将尝试光亲和标记 并对A2-腺苷受体进行生物化学表征。 我们有 开发了两种亚型的有效和相对选择性的抑制剂， 腺苷受体，并基于结构活性关系， 这些抑制剂，我们还将设计和制备高亲和力的配体， 用于表征A1和A2-腺苷受体。

One goal of this program is to prepare irreversible inhibitors of the cAMP-specific and of the calmodulin-sensitive forms of cyclic nucleotide phosphodiesterase. Affinity probes will be used to determine part of the amino acid composition of the hydrolytic site of the calmodulin-sensitive phosphodiesterase. The relationship between irreversible inhibition in intact porcine coronary arteries and the intracellular levels of cyclic AMP and cyclic GMP will be determined in order to establish which form of the enzyme is mainly responsible for the regulation of each nucleotide. In a second aspect of this program, we will attempt to photoaffinity label and biochemically characterize the A2-Adenosine receptor. We have developed potent and relatively selective inhibitors of the two subtypes of adenosine receptor and, based on the structure activity relationships of these inhibitors, we will also design and prepare high affinity ligands to use in characterization of the A1 and the A2-adenosine receptors.