Bridged Peptide Analogue of RA-VII, an Antitumor Bicyclic Hexapeptide
Bridged Peptide Analogue of RA-VII, an Antitumor Bicyclic Hexapeptide
复制标题
RA-VII 的桥接肽类似物，一种抗肿瘤双环六肽
作者：
Hitotsuyanagi;Yukio; Hinosawa;Taka-aki; Nakagawa;Yoshie; Ito;Sho; Lee;Ji-Ean; Hasuda;Tomoyo
设计了RA-VII的桥肽类似物，其中残基1和4的α碳通过四亚甲基链连接以限制18元环肽主链的构象自由度。该肽类似物是通过[1-2-烯丙基甘氨酸-1,1-2-烯丙基甘氨酸-4]RA-VII的闭环复分解反应以及随后所得烯属化合物的氢化来合成的。与RA-VII相比，该类似物对人早幼粒细胞白血病HL-60细胞和人结肠癌HCT-116细胞的细胞毒活性要弱得多，这可能是由于该类似物与RA-VII之间Tyr-6苯环平面方向的差异所致。
A bridged peptide analogue of RA-VII was designed, in which the α carbons of residues 1 and 4 were linked by a tetramethylene chain to restrict the conformational freedom of the backbone of the 18-membered cyclopeptide. This peptide analogue was synthesized by a ring-closing metathesis reaction of [l-2-allylglycine-1,l-2-allylglycine-4]RA-VII and a subsequent hydrogenation of the resulting olefinic compound. Compared with RA-VII, the analogue showed much weaker cytotoxic activity toward human promyelocytic leukemia HL-60 cells and human colon carcinoma HCT-116 cells, which may be accounted for by the difference in the orientation of the Tyr-6 phenyl ring plane between the analogue and RA-VII.