TISSUE SPECIFIC INHIBITORS OF PHOSPHODIESTERASE

该计划的一个目标是制备不可逆转的血管紧张素转换酶抑制剂。 CAMP特异性和钙调蛋白敏感形式的环核苷酸 磷酸二酯酶。亲和力探针将用于确定部分 钙调素敏感蛋白水解区的氨基酸组成 磷酸二酯酶。细胞内不可逆抑制作用与细胞毒性的关系 完整猪冠状动脉与细胞内环磷酸腺苷水平的关系 将确定循环GMP，以确定哪种形式的 酶主要负责对每个核苷酸的调节。 在这个程序的第二个方面，我们将尝试用光亲和标记 以及A2-腺苷受体的生化特征。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，并根据其构效关系 这些抑制剂，我们还将设计和制备高亲和力的配体来 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.