Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Application of heat to aqueous solutions of nucleoside dialdehydes (periodate-oxidized nucleosides) affords the corresponding alpha,beta-unsaturated aldehydes. The reaction was first discovered during studies with adenosine deaminase and was initially investigated enzymatically until the nature of the chemical transformation was determined. A UV peak at 230-250 n, characteristic of the alpha,beta-unsaturated aldehyde group, was obtained by difference spectroscopy and affords a more practical means to study the reaction. Adenosine dialdehyde, obtained by periodate oxidation of adenosine, afforded the same product upon heating as obtained by periodate oxidation of 9-(5-deoxy-beta-D-erythro-ent-4-enofuranosyl)adenine. Further proof of identity was obtained by reduction of these compounds with sodium borohydride and comparison of the dialchols obtained to each other and to a known unsaturated dialcohol. Heating of nucleoside dialdehydes at any time is not recommended. The exact composition of nucleoside dialdehydes used in previous and current biological studies is open to question.
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PMID:Heat-induced formation of alpha,beta-unsaturated nucleoside dialdehydes and their activity with adenosine deaminase. 740 Nov 6

All stereoisomers of adenine and guanine methylene-3-fluoromethylenecyclopropane analogues of nucleosides 9a, 9b, 10a, 10b, 11a, 11b, 12a, and 12b were synthesized and their antiviral activities were evaluated. A highly convergent approach permitted the synthesis of all these analogues using a single intermediate 15. Reaction of aldehyde 13 with fluorotrichloromethane and tri-n-butylphosphine gave fluoroalkenes 14a+14b (83:17). Addition of carbene derived from ethyl diazoacetate gave cyclopropane 15 as the major product. Reduction (19), bromination (20), and phenylselenenylation (21), followed by Se oxidation and beta-elimination gave cis-methylenecyclopropane 22. Addition of bromine provided the reagent 23 for alkylation-elimination. Reaction of 23 with adenine led to an isomeric mixture 25a+26a that after deprotection afforded analogues 9a and 10a. The 2-amino-6-chloropurine furnished 25e+26e and after deblocking (9e and 10e) and hydrolysis gave targets 9b and 10b. Intermediate 15 provided, after debenzylation (27), 2-nitrophenylselenenylation (28), reduction (29), benzylation (30), and oxidation-elimination trans-methylenecyclopropane 31. Addition of bromine gave reagent 32. Further transformations followed the sequence outlined for analogues 9a, 9b, 10a, and 10b. Analogue 9b was effective against human cytomegalovirus (HCMV; Towne) with EC50 2.9 microM. The trans-isomer 10b inhibited AD169 strain of HCMV (EC50 15 microM) and the murine virus MCMV (EC50 2.5 microM). Compound 12a was effective against Epstein-Barr virus (EC50<0.03 microM). Analogue 9a inhibited varicella zoster virus (EC50 5.9 microM) and human immunodeficiency virus type 1 (EC50 5.2 microM). Analogues 9a, 10a, and 11a are moderate substrates for adenosine deaminase. The structure-activity relationships will be discussed in context with other methylenecyclopropane analogues.
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PMID:9-{[3-fluoro-2-(hydroxymethyl)cyclopropylidene]methyl}adenines and -guanines. Synthesis and antiviral activity of all stereoisomers1. 1700 26