Pardin Christophe, Gillet Steve M F G, Keillor Jeffrey W
Département de Chimie, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Que., Canada H3C 3J7.
Bioorg Med Chem. 2006 Dec 15;14(24):8379-85. doi: 10.1016/j.bmc.2006.09.011. Epub 2006 Sep 27.
Herein we report the synthesis and the evaluation of eight novel compounds as irreversible inhibitors of transglutaminase (TGase). These compounds are based on a minimal peptidic scaffold shown previously [Chem. Biol.2005, 12, 469-475] to confer affinity for the TGase active site and bear electrophilic groups such as alpha,beta-unsaturated amide, chloroacetamide or maleimide; their general structure being Cbz-Phe-spacer-electrophile. The affinity conferred by the Cbz-Phe scaffold was determined by comparison to N-propylacrylamide and the length of the spacer was also varied to evaluate its importance. The inhibitory efficiencies (k(inact)/K(I)) of these compounds vary up to 10(5)M(-1)min(-1), among the highest reported for derivatives based on this simple Cbz-Phe peptidic scaffold.
在此，我们报告了8种新型化合物的合成及其作为转谷氨酰胺酶（TGase）不可逆抑制剂的评估。这些化合物基于先前[《化学生物学》2005年，12卷，469 - 475页]所示的最小肽骨架，该骨架赋予对TGase活性位点的亲和力，并带有亲电基团，如α，β - 不饱和酰胺、氯乙酰胺或马来酰亚胺；它们的一般结构为Cbz - Phe - 间隔基 - 亲电试剂。通过与N - 丙基丙烯酰胺比较来确定Cbz - Phe骨架赋予的亲和力，并且间隔基的长度也有所变化以评估其重要性。这些化合物的抑制效率（k(inact)/K(I)）变化高达10(5)M(-1)min(-1)，是基于这种简单Cbz - Phe肽骨架的衍生物所报道的最高值之一。
