A series of 5-spirocyclopropanobarbiturates bearing alkyl and aryl su bstituents on the cyclopropane ring has been synthesized. Dihydro-orotate dehydrogenase from Clostridium oroticum was shown to be inhibited by these compounds. A related series of 5-membered-ring compounds (hydantoins and pyrazoles) was prepared but all the compounds were found to be inactive. In order to correlate these observations with previous resu Its concerning 5arylmet hy I hydantoi ns and 5aryl idenehydantoins as inhibitors, 5-arylidenebarbiturates were also assessed as inhibitors and found t o be the most active of the compounds investigated. The results are interpreted in the context of molecular recognition by this enzyme and the possibility of using substrate surrogates as templates for constructing latent inhibitors of enzymes.

An attempt is made to create a basis for the understanding offlavin-(Vitamin B2-) dependent oxidations in terms of molecular structure. The main points of this survey can be summarized as follows: a) Theflavins must be differentiated according to their redox states (quinone state, radical state, hydroquinone state), since configuration, energy content of the tautomeric forms, metalaffinity etc., alter drastically during reduction. -6 ) The methylgroup on C-8 of the flavoquinone is reactive. -cj The electron transfer properties of the flavin system frequently depend on the coupling of secondary redox systems to the apoprotein. This interaction thermodynamically stabilizes the half-reduced state of the flavin. -d) Numerous novel ffavin types, among them stabilized free radicals, have become availabIe through syntheses at the dihydro stage. -ej Reaction of the flavin radical with 0 2 is slow as long as no disproportionation occurs, i. e. the fast flavin autoxidation proceeds via the dihydro state.f l The flavin nucleus gains affinity for heavy metal ions only by the acceptance of one, and only one, electron. -g) Redox activity and contact with the ffavin coenzyme have been confirmed for Fe and Mo, which occur in flavoproteins. The properties of the metal coordination sphere are determined primarily by sulfur-containing groups of the apoprotein.

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The synthesis and reactions of various 8-substituted lumazine derivatives are described. In particular, it is shown that these compounds readily undergo hydration, and that the resulting carbinol-amines can take part in reactions which involve ring-opening in the pyrazine ring. These studies are extended to demonstrate a new chemical synthesis of riboflavin and related isoalloxazines from 8-substituted pteridine derivatives. A possible mechanism for this reaction, which is analogous to that involved in the biosynthesis of riboflavin, is discussed. Similar reactions of 2-iminopteridine derivatives are described.

We describe two enzyme-linked immunosorbent assays for rotavirus antigen in feces, which were designed to be as sensitive and specific as possible, and easy to use anywhere. Both are indirect methods, using the antibody capture method, but the second assay utilizes a rotavirus group-specific monoclonal "detecting" antibody instead of the hyperimmune polyvalent guinea pig antisera used in the first assay. Both tests weîe found to be more sensitive than electron microscopy for detecting virus. To develop these tests, solid phase, antiserum production methods, treatment of the test antigen with EDTA, substrate, stability of reagents, and the need for confirmatory "blocking" tests were all examined. The first assay described is that used at present by the World Health Organization for their worldwide diarrheal disease control program.