Zanotti G, D'Auria G, Paolillo L, Trivellone E
Biochim Biophys Acta. 1986 Apr 22;870(3):454-62. doi: 10.1016/0167-4838(86)90253-0.
The effect of substitution of L and D amino acids in amatoxin analogues is discussed in this paper. The structure of the analog where D-alanine substitutes for glycine in position 7 has been worked out in solution by two-dimensional NMR methods using a 500 MHz instrument. The combined use of COSY and NOESY two-dimensional spectra allows a clear assignment of the resonances. The use of the coupling constants permits the calculation of the phi angles of the backbone. The NOE effects reveal the through-space contacts between protons of different peptide units, thus determining the rigidity of the amatoxin structure. On these grounds it has been possible to elucidate the conformation of the amatoxin analogue that resembles very closely that of beta-amanitin, thus explaining the high inhibitory activity toward RNA polymerase B.
本文讨论了鹅膏毒素类似物中L-氨基酸和D-氨基酸取代的影响。通过使用500 MHz仪器的二维核磁共振方法，已在溶液中确定了7位甘氨酸被D-丙氨酸取代的类似物的结构。COSY和NOESY二维光谱的联合使用使得能够清晰地归属共振信号。耦合常数的使用允许计算主链的φ角。NOE效应揭示了不同肽单元质子之间的空间接触，从而确定了鹅膏毒素结构的刚性。基于这些依据，已经能够阐明与β-鹅膏菌素非常相似的鹅膏毒素类似物的构象，从而解释了其对RNA聚合酶B的高抑制活性。
