Hideyuki Konishi

Negative regulation of the RIG-I signaling by the ubiquitin ligase RNF125

Retinoic acid-inducible gene I (RIG-I) plays a pivotal role in the regulation of cytokine production induced by pathogens. The RIG-I also augments the production of IFN and other cytokines via an amplification circuit. Because the production of cytokines is closely controlled, up- and down-regulation of RIG-I signaling also needs strict regulation. The mechanism of this regulation, however, remains elusive. Here, we found that RIG-I undergoes proteasomal degradation after conjugation to ubiquitin by RNF125. Further, RNF125 conjugates ubiquitin to MDA5, a family protein of RIG-I as well as IPS-1, which is also a downstream protein of RIG-I signaling that results in suppressing the functions of these proteins. Because RNF125 is enhanced by IFN, these functions constitute a negative regulatory loop circuit for IFN production.

Cycloaddition reactions of 6-cyanobenz[a]indolizines with activated alkynes. Formation of benzo[2.2.3]- and [2.3.4]cyclazines

Cycloaddition reactions of 6-cyanobenz[a]indolizines with activated alkynes such as dimethyl acetylenedicarboxylate, diacetylacetylene, methyl propiolate, methyl trimethylsilylpropiolate, methyl phenylpropiolate, and 4-phenyl-3-butyn-2-one were investigated.

Site selectivity in the 1,3-dipolar cycloaddition reaction of unsymmetric pyridinium bis(methoxycarbonyl)methylides with methyl propiolate

The 1,3-dipolar cycloaddition of unsymmetric pyridinium bis(methoxycarbonyl)methylides with methyl propiolate proceeds in moderate to good yields with high to moderate site selectivity with respect to the ylide. Polar 3-substituted pyridinium bis(methoxycarbonyl)methylides generally gave predominantly the corresponding 8-substituted indolizines regardless of the substituents. The results can be explained by dipole-dipole interactions

The Electronic Structure of Several Reaction Intermediates

二,三の興味ある反応中間体の電子状態の検討を行なうため,extended Huckel法によって計算を行なった。とりあつかった化合物は,トランス型,シス型アセチレン,ベンザインおよびその類似化合物(ナフタリイン,シクロペンタイン),プロトン化エチレンおよびベンゼニウムイオンである。計算の結果,屈曲型アセチレンには炭素原子に局在化した特異なσ型軌道が現われ,これが不安定性に寄与すること,またべンザインおよびその類似化合物もシス型アセチレンと同様な準位をもち,三重結合に近い性格をもつこと,などが明らかとなった。プロトン化エチレンについても付加位置の変化に伴う電子状態の変化を検討し,ベンゼニウムイオンについては,プロトン付加によるベンゼン環構造の変化を考慮して計算を行ない,従来の他の方法による計算結果と良好な並行関係をもつことが示された。