Demuth H U, Schlenzig D, Schierhorn A, Grosche G, Chapot-Chartier M P, Gripon J C
Department of Biochemistry, Martin-Luther-University of Halle, Saale, Germany.
FEBS Lett. 1993 Mar 29;320(1):23-7. doi: 10.1016/0014-5793(93)81649-k.
A novel class of competitive, acylating inhibitors for the proline-specific peptidases: dipeptidyl peptidase IV, dipeptidyl peptidase II and prolyl endopeptidase, has been developed. The inhibitor molecules combine the efficacy of aminoacyl pyrrolidides and the potential transacylating capability of diacyl hydroxyl amines. The N-terminal deblocked inhibitors are potent reversible inhibitors of porcine kidney dipeptidyl peptidase IV, human placenta dipeptidyl peptidase II exhibiting Ki values in the microM range. Boc-protected (omega-N-hydroxy acyl amid) aminodiacarboxylic acid pyrrolidides inhibit substrate hydrolysis by prolyl endopeptidases from different sources competitively reaching Ki values of 30 nM to 60 microM. Additionally, alpha-N-BOC-(omega-N-hydroxy acetyl) glutaminyl pyrrolidide modifies human placenta prolyl endopeptidase in a time-dependent reaction.
二肽基肽酶IV、二肽基肽酶II和脯氨酰内肽酶。抑制剂分子结合了氨酰基吡咯烷的功效和二酰基羟胺的潜在转酰基能力。N-末端去封闭的抑制剂是猪肾二肽基肽酶IV的有效可逆抑制剂，人胎盘二肽基肽酶II的Ki值在微摩尔范围内。Boc保护的（ω-N-羟基酰基酰胺）氨基二羧酸吡咯烷竞争性抑制来自不同来源的脯氨酰内肽酶对底物的水解，Ki值为30 nM至60 μM。此外，α-N-BOC-（ω-N-羟基乙酰基）谷氨酰胺基吡咯烷在时间依赖性反应中修饰人胎盘脯氨酰内肽酶。
