The acetamidomethyl (Acm) group is a widely used protecting group for the thiol of cysteine during the SPPS process. We prepared the amino terminal loop of the snake alpha-neurotoxin, [Cys3,Cys23, Ser17](1-24) amide, from the linear peptide [Cys(Acm)3,23,Ser17](1-24) amide obtained by SPPS. Three different methods of deprotection of Cys(Acm) and disulfide bond formation were used: iodine, thallium(III) trifluoroacetate and mercuric acetate/potassium ferricyanide. The iodine method failed to yield the expected peptide, and gave instead the mono-iodinated tyrosine analog. The disulfide cyclized peptide obtained by thallium (III) or Hg(II) procedures displayed a MW value observed by mass spectrometry that was higher than the calculated value. The difference (MWobs-MWcalc) corresponded to a multiple of the Acm moiety, which is shifted intra- and/or intermoleculary. Furthermore, we observed, in addition to the Acm shift in the disulfide cyclized decapeptide with a highSer and Thr content (model peptide II), the dimerization phenomenon in the Tl(TFA)3 process. Therefore we conclude that a side reaction, a S--O(Ser,Thr) Acm shift, occurred during the Cys(Acm) deprotection. This shift was supported by the demonstration of Ser(O-Acm) formation in the reaction of Boc-(L)-Cys(Acm) with Tl(TFA)3 in the presence of an equimolar amount of (L)Ser. We report here the efficiency of a trivalent alcohol, glycerol, as scavenger in the both Tl(TFA)3 and mercuric/ferricyanide methods, in an attempt to circumvent this side-reaction during the disulfide bond formation step starting from a bis-Cys(Acm) peptide with a high Ser and Thr content, such as the N-terminal loop of neurotoxin, model peptide II or a similar peptide.

中文翻译：

---

高丝氨酸和苏氨酸含量的肽中（S-乙酰氨基甲基）半胱氨酸脱保护过程中的副反应

乙酰氨基甲基（Acm）基团是SPPS过程中半胱氨酸硫醇的广泛使用的保护基团。我们从通过以下方法获得的线性肽[Cys（Acm）3,23，Ser17]（1-24）酰胺制备了蛇α-神经毒素[Cys3，Cys23，Ser17]（1-24）酰胺的氨基末端环SPPS。Cys（Acm）脱保护和二硫键形成的三种不同方法：碘，三氟乙酸th（III）和乙酸汞/铁氰化钾。碘法不能产生预期的肽，而是给出了单碘化酪氨酸类似物。通过th（III）或Hg（II）程序获得的二硫键环化肽显示出的质谱值高于计算值。差异（MWobs-MWcalc）对应于Acm部分的倍数，它在分子内和/或分子间移动。此外，我们观察到，除了具有高Ser和Thr含量的二硫化物环化的十肽中的Acm移位（模型肽II）之外，Tl（TFA）3过程中还存在二聚现象。因此，我们得出结论，在Cys（Acm）脱保护过程中发生了S-O（Ser，Thr）Acm移动的副反应。在等摩尔量的（L）Ser存在下Boc-（L）-Cys（Acm）与Tl（TFA）3的反应中Ser（O-Acm）形成的证明支持了这种转变。我们在这里报告了三价醇甘油作为Tl（TFA）3和汞/铁氰化物方法中的清除剂的效率，试图避开从bis-Cys（ Acm）肽，具有较高的Ser和Thr含量，