The cyclic purine nucleotides 3’, 5’-c AMP and 3’, 5’-c GMP are well-established second messengers. c GMP has recently been covered in a volume of the Handbook of Experimental Pharmacology (volume 191). In addition to 3’, 5’-c AMP and 3’, 5’-c GMP, so-called non-canonical cyclic nucleotides exist. These comprise the cyclic pyrimidine nucleotides 3’, 5’-c CMP and 3’, 5’-c UMP, the purine nucleotide 3’, 5’-c IMP, the 2’, 3’-nucleoside monophosphates and cyclic dinucleotides. In this volume of the Handbook of Pharmacology, word-leading experts in the field summarize our current knowledge on these non-canonical cyclic nucleotides, discuss open questions, future research directions and the pharmacotherapeutic implications. Special emphasis will be given to the emerging roles of 3’, 5’-c CMP and 3’, 5’-c UMP as second messengers with regard to generators, effectors, biological functions, inactivation and bacterial toxins. The role of 3’, 5’-c IMP as potential second messenger will also be critically discussed. Furthermore, we will consider transport of cyclic nucleotides and their potential role as first messengers. The role of the cyclic dinucleotide c GAMP in the immune system will covered, too. Lastly, the book will present important methodological aspects ranging from mass-spectrometric methods for cyclic nucleotide detection to the synthesis of nucleotide analogs as experimental tools and holistic methods for analysis of cyclic nucleotide effects.
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Part I: 3’, 5’-c CMP and 3’, 5’-c UMP as second messengers: c CMP and c UMP across the tree of life: From c CMP and c UMP generators to c CMP- and c UMP-regulated cell functions.- c CMP and c UMP in apoptosis: Concepts and methods.- Mammalian nucleotidyl cyclases and their nucleotide binding sites.- The
Pseudomonas aeruginosa exoenzyme Y: A promiscuous nucleotidyl cyclase edema factor and virulence determinant.- Cyclic nucleotide monophosphates in plants and plant signalling.- c AMP-dependent protein kinase and c GMP-dependent protein kinase as cyclic nucleotide effectors.- Regulation of HCN ion channels by non-canonical cyclic nucleotides.- Identification of c CMP and c UMP substrate proteins and cross-talk between c NMPs.- Inactivation of non-canonical cyclic nucleotides: Hydrolysis and transport.-
Part II: 3’, 5’-c IMP, 8-nitro-c GMP, 2’, 3’-c NMPs and cyclic dinucleotides as signaling molecules: 3’, 5’-c IMP as potentialsecond messenger in the vascular wall.- The discovery of 2’, 3’-c NMPs in mammalian systems: From rodents to humans.- 8-Nitro-c GMP: A novel protein-reactive c NMP and its emerging roles in autophagy.- Cyclic dinucleotides in the scope of the mammalian immune system.-
Part III: Methods/Tools for c NMP research: Mass-spectrometric analysis of non-canonical cyclic nucleotides.- Medicinal chemistry of the noncanonical cyclic nucleotides c CMP and c UMP.-
Holistic methods for the analysis of c NMP effects.- The chemistry of the non-canonical cyclic dinucleotide 2’3′-c GAMP and its analogs.
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