Steroidogenic and lipolytic activities of 8-substituted derivatives of cyclic 3',5'-adenosine monophosphate

Synthesis and biochemical studies of various 8-substituted derivatives of guanosine cyclic-3',5' phosphate, inosine cyclic-3',5' phosphate, and xanthosine cyclic-3',5' phosphate

“…The significant activity of some of the cGMP derivatives in the histamine-induced bronchospasm and the passive cutaneous anaphylaxis systems suggests that the analogs are entering cells (M. Van Winkle and L. N. Simon, unpublished results). The activity of several 8-substituted derivatives of cAMP in isolated cells (Free et al, 1971) and in tissue preparations (Rubin et al, 1971) suggests that cyclic nucleotides do penetrate cells. With few exceptions, the 8-substituted derivatives of cGMP (1), cIMP (12), cXMP (10), and cAMP (22) were resistant to enzymatic hydrolysis by a rabbit kidney 3',5'-cyclic nucleotide phosphodiesterase preparation.…”

Conditions that elevate intracellular cyclic AMP levels promote spore formation in Dictyostelium

“…Under these conditions, 8-Br-cAMP has negligible effects on cell surface receptors. This, combined with the enhanced ability of the analog to cross cell membranes [12] and activate cAMPdependent protein kinase [l I] strongly suggest that 8-Br-CAMP promotes spore formation by mimicking cAMP inside the cell. Third, cells exposed to 5 mM caffeine or 0.1 mM progesterone during in vitro differentiation form only stalk cells [45], but simultaneous exposure to 8-Br-CAMP restored spore formation to near-normal levels ( Table 1).…”

Synthesis and biological activity of some purine 5'-thio-5'-deoxynucleoside 3',5'-cyclic phosphorothioates

“…By comparison, the doubly modified cAMP derivative, 5 '-thio-cIMP, exhibited have been interested in the effects of modification of the purine (Muneyama et al, 1971;Bauer et al, 1971;Meyer et al, 1972), carbohydrate (Miller et al, 1973), and phosphate moieties (Meyer et al, 1973) of 3',5'-cyclic nucleotides on biological activity in cyclic nucleotide dependent enzyme systems. Although several reports have appeared concerning the effect of heterocyclic modification of 3',5'-cyclic nucleotides on the resulting biological activity (Muneyama et al, 1971;Bauer et al, 1971;Meyer et al, 1972;Drummond and Severson, 1971;Free et al, 1971;and Anderson et al, 1972), few reports have dealt with alterations at the cyclic phosphate moiety. Compounds which involve structural modification of the cyclic phosphate moiety, such as substitution of an exocyclic oxygen by either nitrogen (Meyer et al, 1973) or sulfur (Eckstein, 1970), or the substitution of an endocyclic oxygen by either methylene (Jones et al, 1970) or nitrogen (Murayama et al, 1971), have been shown to be either extremely weak or inactive in the activation of phosphorylase b kinases (Drummond and Powell, 1970) or cyclic nucleotide dependent protein kinases (Kuo and Greengard, 1970), or in the stimulation of synthesis of inducible enzyme messenger RNA (Anderson et al, 1972).…”