AMP analogues

Consistent with the experimental data, mutation of the purine base nitrogens, i.e. N, 3N, 7N and 9N, showed that replacement of N, 3N and 9N with CH had little effect on binding affinity whereas a similar replacement of 7N led to a loss of 2.8 kcal/mol. The 0.6 kcal/mol gain in affinity for the 1-deaza and 3-deaza AMP analogues was consistent with the hydrophobic nature of this portion of the binding site cavity and the absence of hydrogen bond donors in the vicinity of either heteroatom. 

Cyclic indolicidin peptide derivative with higher charge NC12-K4S4(l-13)a, dermaseptin AMP analogue K4-S4(l-13)a, dermaseptin truncated antimicrobial analogue... 

New cyclic AMP analogues have been prepared by phosphorylation of the sulfur analogue of adenosine (31) (Scheme 9) (82LA651). 

Cyclic AMP is one of the mediators of FSH action on LH receptor induction because dibutyryl cyclic AMP will increase granulosa receptors in vitro. Other factors may also be involved (e.g., oestrogens) because the cyclic AMP analogues were less potent than FSH. Once induced, the continual presence of FSH is required to maintain normal levels of LH receptors [5],... 

Extracellular calcium is required to give maximum LH stimulated steroidogenesis in isolated Leydig cells [15,18]. Using the intracellular fluorescent calcium indicator, Quin 2, it has been shown that lowering the extracellular calcium concentration from 2.5 mM to 1.1 xM lowered the LH stimulated intracellular calcium concentrations from 300-500 nM to only 52 nM. These studies showed that LH increases intracellular calcium and that this increase is dependent mainly on extracellular levels of calcium. Cyclic AMP analogues were also shown to increase intracellular calcium to the same concentrations as those obtained with LH, indicating that cyclic AMP is one of the mediators of LH action on calcium mobilization [15]. 

ACTH stimulates the synthesis of steroids by the cells of the adrenal cortex. The steroidogenic action of ACTH is mediated primarily by the intracellular messenger cyclic AMP acting via cyclic AMP-dependent protein kinase. The evidence for this is that (i) ACTH stimulates cyclic AMP production in intact adrenocortical cells and in plasma membrane preparations (ii) cyclic AMP analogues added to adrenocortical cells stimulate steroidogenesis to the same extent as ACTH and (iii) mutant adrenocortical cells with defective cyclic AMP-dependent protein kinase lack stimulation of steroidogenesis by ACTH [2],... 

The nature of the second messenger(s) involved in the action of prolactin on Nb2 cells has been studied [108]. Levels of intracellular cyclic AMP do not change when the cells are treated with prolactin, and cyclic AMP analogues and phosphodiesterase inhibitors do not induce proliferation. Similarly, no clear evidence could be obtained for a clear-cut involvement of prostaglandins in Nb2 cell proliferation. 

Figure 7-14. Elution of lactate dehydrogenase (LDH) isozymes with a concave gradient of NADH. Protein, 0.2 mg, in 0.2 ml O.IM sodium phosphate buffer, pH 7.0, ImM /3-mercaptoethanol, and IM NaCl was applied to an AMP analogue-sepharose column (140 X 6 mm, containing 2.5 g wet gel) equilibrated with O.lM sodium phosphate buffer, pH 7.5. The column was washed with 10 ml of the latter buffer, then the isozymes were eluted with a concave gradient of 0.0 to 0.5mM NADH in the same buffer, containing ImM /3-mercaptoethanoI. Fractions of 1 ml were collected at a rate of 3.4ml/hour. The hatched area indicates the pooled fractions that were rechromatographed. [From P. Brodelius and K. Mosbach, FEBS Lett, 35 223 (1973).]...

Figure 14.8. Bioelution of LDH isoenzymes from a Sepharose AMP affinity column using a concave NADH gradient. [Reprinted, by permission, from P. Brodelius and K. Mosbach, FEBS Lett. 35, 1973, 223-226. Separation of the Isoenzymes of Lactate Dehydrogenase by Affinity Chromatography Using an Immobilized AMP-Analogue . The exclusive for all languages and countries is vested in the Federation of European Biochemical Societies.]...

Henin, N. Vincent, M.F. Van den Berghe, G. Stimulation of rat liver AMP-activated protein kinase by AMP analogues. Biochim. Biophys. Acta, 1290, 197-203 (1996)... 

Weekes, J. Hawley, S.A. Gorton, J. Shugar, D. Hardie, D.G. Activation of rat liver AMP-activated protein kinase by kinase kinase in a purified, reconstituted system. Effects of AMP and AMP analogues. Eur. J. Biochem., 219, 751-757 (1994)... 

Dolphin A, Archer E. An adenosine agonist inhibits and a cyclic AMP analogue enhances the release of glutamate but not GABA from slices of rat dentate gyrus. Neurosci Lett 1983 43 49-54. 

Cyclic AMP analogues have been prepared from pyrazolo[3,4-d]... 

Lo, K.W, et al., 2012. The small molecule PKA-speciflc cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization. Journal of Tissue Engineering and Regenerative Medicine 6,408 17. 

The AMP analogue 143 has been described, along with the similar analogues of thynoidine 5 - and 3 -monophosphates. Another paper describes a range of S -O-phosphonates of ribonucleosides and deoxyribonucleosides, and also the S -O-phosphonomethyl con unds 145 (B=Thy, Ade), prepared from 144 by treatment with The carbocyclic phosphonate... 

Conformational studies by n.m.r. spectroscopy and/or computational methods have also been reported for the 1-deoxy-psicofuranosyl nucleoside 8, 2 - and 3 -substituted 2, 3 -dideoxyribonucleosides, 2-substituted (F,C1) adenosines and selected confcxmers of 2,3-didehydro-1,2,3-trideoxy-p-D-ribofuranosylamine, and for the AMP analogue 5 -0-[A/-(L-alanyl)sulfamoyl]adenosine (9) in solution. Compound 9 proved to be more flexible then anticipated from an X-ray structure analysis. ... 

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