Formycin structure

The molecule 7-aminopyrazolopyrimidine is related to the DNA base adenine. It is the base attached to ribose in formycin A, which is believed to have potential therapeutic value. It is also shown in Figure 5. There is a paradox in this system. This molecule is deactivated by the enzyme adenosine deaminase (ADA). In solution the N7H tautomer predominates. This structure however inhibits ADA, and this tautomer of formycin A would not be deactivated by the enzyme. 

Grouped in this Section are the C-D-pentofuranosyl-imidazoles, -pyrazolopyrimidines, and -adenines. The last two analogs are positional isomers of formycin in which the heterocyclic moiety is attached to the sugar at an unnatural position. A rationale103 for the synthesis of this type of analog is of interest it was based on the possibility of a close structural similarity between a natural adenine nucleoside and synthetic analog with respect to available hydrogenbonding sites. 

Certain fluorescent compounds, such as formycin nucleotides and eosin, behave as noncovalently binding ATP analogs, and their fluorescence increases upon association with the ATPases. The transition from the Na+-form to the K+-form of Na+-K+-ATPase gives rise to a decrease in fluorescence from these probes. The fluorescence of fluorescein isothiocyanate (FITC) bound covalently at the nucleotide site of Na+-K+-ATPase (Table 3) also decreases in relation to transition from the Na+-form to the K+-form. With the noncovalent as well as with the covalently-binding probes the fluorescence decrease probably reflects the structural change in the nucleotide site associated with the reduced nucleotide affinity in the E2 form (see above). By contrast, when FITC is attached to the SR Ca2+-ATPase (at the residue homologous to the FITC-binding residue in Na+-K+-ATPase) the fluorescence increases upon removal of Ca2+. Most likely this relates to the above discussed difference between Na+-K+-ATPase and Ca2+-ATPase with respect to the existence of a stable E2 form with low affinity for nucleotide. 

Protonation at N(4) and N(6), and deprotonation at N(l) have been described for formycin [90JOC753 94MI(13)481]. The X-ray structural data on protonated formycin are surprisingly heterogeneous whereas formycin hydrobromide was reported as the N6(H),2H form [74AX(B)1511], 3 -deoxyformycin hydrobromide was detected as the N4(H),1H tautomer [87AX(C)2358],... 

Figure 4.14 Comparison of structures of adenosine and its fluorescent analog formycin A.

Figure 17-7. Structures of adenosine and related nucleosides which serve as substrates for S-adenosyl-L-homocysteine hydrolase. 1, Adenosine 2, formycin A 3, neburalin 4, adenosine Af-oxide 5, 2-chloroadenosine 6, tubercidine 7, N6-methyladenosine 8, inosine 9, 1-methyladenosine.

Compounds structurally related to adenosine 5 -triphosphate also exhibit inhibition. Among adenosine 5 -pyrophosphate, adenosine 5 -phos-phate, adenosine, and adenine, adenosine showed the strongest inhibition. This result indicated that the adenine and n-ribose moieties of adenosine 5 -triphosphate bind with the enzyme. Formycin A is an analog of adenosine, and exhibits inhibition (61% at 3.2 mM) formycin B is less active. This suggested that the amino group of adenosine binds with the... 

Improved syntheses of showdomycin and 2 -deoxyshowdomycin have been described, and the paper includes an X-ray single crystal structure for l-benzyl-2 -deoxyshowdomycin. The pH dependence of the chemical shifts of formycin has been investigated, and conformational conclusions drawn. ... 

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