Bhuta P, Chung H L, Hwang J S, Zemlicka J
J Med Chem. 1980 Dec;23(12):1299-305. doi: 10.1021/jm00186a004.
Circular dichroism spectra of series of chloramphenicol derivatives la-r were measured in water at pH 7. Compounds 1a-o exhibit two positive Cotton effects at 310--340 and 240--260 nm, respectively, and a weaker negative Cotton effect at 280--300 nm. In analogues 1c, 11, and 1m there is only a minimum between the two positive Cotton effects. Derivatives 1p--r possess a strong negative Cotton effect at ca. 280 nm. Compounds 1a--r were examined as inhibitors of the puromycin reaction with Escherichia coli 70S ribosome-poly(U)-N-AcPhe-tRNA complex. Analogues 11, 1n, lo, and lq are potent competitive inhibitors of puromycin comparable to or better than chloramphenicol (1b). Compounds 1k and 1m are less active, whereas 1d--g and 1j are only moderately effective. The rest of the analogues have marginal or no activity. The results are compared with previous biological data and discussed in terms of a retro-inverso relationship of chloramphenicol (1b) to the aminoacyl moiety of puromycin (aminoacyl-tRNA) and to a hypothetical transition state of peptide bond formation.
在pH 7的水中测量了一系列氯霉素衍生物1a - r的圆二色光谱。化合物1a - o分别在310 - 340 nm和240 - 260 nm处呈现两个正科顿效应，在280 - 300 nm处有一个较弱的负科顿效应。在类似物1c、11和1m中，两个正科顿效应之间只有一个极小值。衍生物1p - r在约280 nm处有一个强负科顿效应。研究了化合物1a - r作为嘌呤霉素与大肠杆菌70S核糖体 - 聚（U） - N - 乙酰苯丙氨酸 - tRNA复合物反应的抑制剂。类似物11、1n、1o和1q是嘌呤霉素的有效竞争性抑制剂，与氯霉素（1b）相当或更好。化合物1k和1m活性较低，而1d - g和1j只是中等有效。其余类似物的活性很小或没有活性。将结果与先前的生物学数据进行了比较，并根据氯霉素（1b）与嘌呤霉素（氨酰 - tRNA）的氨酰基部分以及肽键形成的假设过渡态的反式 - 反式关系进行了讨论。
