63 光反応性インドールアルカロイド発癌プロモーター : 合成、生物活性、光アフィニティーラベリング(ポスター発表の部)

概要

論文の詳細を見る
Teleocidins are potent tumor promoters produced by actinomycetes. To investigate the target proteins of teleocidins, photoaffinity labeling on the mouse epidermal particulate fraction, the target tissue of teleocidins, was attempted. Three new photolabile teleocidin derivatives (Az-A-1, Az-C_7 and Az-C_2) were synthesized from teleocidin A-1 (14) or (-)-indolactam-V (1), and examined for three in vitro bioassays related to tumor-promoting activity. These were binding affinity to the 12-O-tetradecanoylphorbol-13-acetate receptor in the mouse epidermal particulate fraction, activation of protein kinase C (PKC) and ability to enhance incorporation of inorganic phosphate into phospholipids of HeLa cells. Az-A-1 (15) and two epimers of Az-C_7 (11a,11b) were 10 to 100-fold more active than (-)-indolactam-V (1), the fundamental structure of teleocidins. Synthesis of the ^3H-labeled probes with specific activity of more than 40Ci/mmol was achieved by use of commercially available ^3H-labeled succinimidyl-4-azidobenzoate. Specific binding of [^3H]Az-A-1 and [^3H]Az-C_7 to the mouse epidermal particulate fraction was saturable at approximately 20nM. Photoaffinity labeling on the particulate fraction using [^3H]Az-A-1 supported the recent hypothesis that the alkyl chain at position 7 of teleocidins is involved in the interaction with the phospholipids close to the receptor site. SDS gel electrophoresis of the photolabeled particulate fraction suggested the existence of some proteins specifically photolabeled by [^3H]Az-A-1 and [^3H]Az-C_7. However, PKC, the major target site of teleocidins, was not significantly photolabeled possibly because the content of PKC in the particulate fraction is very low.
天然有機化合物討論会の論文
1993-09-10

63 光反応性インドールアルカロイド発癌プロモーター : 合成、生物活性、光アフィニティーラベリング(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク