Design and synthesis of biotin analogues reversibly binding with streptavidin
Design and synthesis of biotin analogues reversibly binding with streptavidin
复制标题
与链霉亲和素可逆结合的生物素类似物的设计与合成
DOI：
10.1002/asia.201500120
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Motomu Kanai
中科院分区：
文献类型：
--
作者：
Tomohiro Yamamoto;Kiyoshi Aoki;Akira Sugiyama;Hirofumi Doi;Tatsuhiko Kodama;Yohei Shimizu;Motomu Kanai
合成了两个新的生物素类似物生物素碳酸酯5和生物素氨基甲酸酯6。这些分子被设计成通过用氧取代生物素的环状尿素部分的氢键供体NH基团(S)来与链霉亲和素可逆结合。以3，4-顺式二羟基团提供所需立体化学的阿拉伯糖(7)为原料合成了生物素碳酸酯5，总收率为11 %(超过10 步骤)。生物素氨基甲酸酯6的合成由半胱氨酸手性醛33以11 %的总收率完成(超过7 步骤)。水溶性生物素碳酸酯类似物46和生物素氨基甲酸酯类似物47的表面等离子体共振分析表明，这两种化合物与链霉亲和素结合的KD值分别为6.7×10−6M和1.7×10−10M。这些值明显大于生物素(Kd=10−15M)，表明氮原子对生物素与链霉亲和素的强结合具有重要意义。
Two new biotin analogues, biotin carbonate5and biotin carbamate6, have been synthesized. These molecules were designed to reversibly bind with streptavidin by replacing the hydrogen‐bond donor NH group(s) of biotin’s cyclic urea moiety with oxygen. Biotin carbonate5was synthesized fromL‐arabinose (7), which furnishes the desired stereochemistry at the 3,4‐cis‐dihydroxy groups, in 11 % overall yield (over 10 steps). Synthesis of biotin carbamate6was accomplished fromL‐cysteine‐derived chiral aldehyde33in 11 % overall yield (over 7 steps). Surface plasmon resonance analysis of water‐soluble biotin carbonate analogue46and biotin carbamate analogue47revealed thatKDvalues of these compounds for binding to streptavidin were 6.7×10−6Mand 1.7×10−10M, respectively. These values were remarkably greater than that of biotin (KD=10−15M), and thus indicate the importance of the nitrogen atoms for the strong binding between biotin and streptavidin.