Van Beeumen J, Devreese B, Ghanem G, Lejeune F, Deknop C, Faignet C, Toch I, Jacquemotte F
State University of Gent, Belgium.
Pept Res. 1994 Jan-Feb;7(1):7-12.
Two different chlorinated drugs, chlorambucil and melphalan, have been linked to the carrier alpha-melanocyte-stimulating hormone at the end of the solid-phase peptide synthesis of the hormone. The [Nle4, D-Phe7] and the [Nle4, L-Phe7] derivatives of the hormone have both been used. It was found by electrospray mass spectrometric analysis that the products undergo hydrolysis of the chlorinated moiety of the drugs, most likely due to the acidic conditions necessary for cleavage of the peptide from the resin. Only the melphalan-O(ethyl)-N(succinyl)-derivative of alpha-melanocyte-stimulating hormone [Nle4, L-Phe7] did not show a bis-hydroxylated form. It was proven by blank experiments with commercially available melphalan that this mustard occurs for some 45%-50% in the mono-hydroxylated form, which is known to be pharmacologically poorly active.
两种不同的氯化药物，苯丁酸氮芥和美法仑，在激素的固相肽合成结束时与载体α-黑素细胞刺激素相连。该激素的[Nle4, D-Phe7]和[Nle4, L-Phe7]衍生物均已被使用。通过电喷雾质谱分析发现，产物会发生药物氯化部分的水解，这很可能是由于从树脂上裂解肽所需的酸性条件所致。只有α-黑素细胞刺激素[Nle4, L-Phe7]的美法仑-O(乙基)-N(琥珀酰)-衍生物未显示双羟基化形式。通过使用市售美法仑进行的空白实验证明，这种芥子气约45%-50%以单羟基化形式存在，已知其药理活性较差。
