Inhibition of the elastase of Pseudomonas aeruginosa by N alpha-phosphoryl dipeptides and kinetics of spontaneous hydrolysis of the inhibitors.
Inhibition of the elastase of Pseudomonas aeruginosa by N alpha-phosphoryl dipeptides and kinetics of spontaneous hydrolysis of the inhibitors.
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DOI：
10.1021/bi00307a036
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发表时间：
1984-06
期刊：
影响因子：
2.9
通讯作者：
L. Poncz;Thomas A. Gerken;Dorr G. Dearborn;Damian Grobelny;Richard E. Galardy
中科院分区：
文献类型：
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作者：
L. Poncz;Thomas A. Gerken;Dorr G. Dearborn;Damian Grobelny;Richard E. Galardy
通过质子核磁共振光谱跟踪N-[（α-L-吡喃鼠李糖氧基）磷酸基]-L-亮氨酰-L-色氨酸（phosphoramidon）、N α-磷酰基-L-亮氨酰-L-色氨酸（PO 3LeuTrp）、N α-磷酰基-L-亮氨酰-L-苯丙氨酸（PO 3LeuPhe）和N α-磷酰基-L-亮氨酰-L-苯丙氨酰胺（PO 3LeuPheNH 2）的水解速率。PO 3LeuTrp、PO 3LeuPhe和PO 3LeuPheNH 2的水解速率（kobsd）在研究的pH范围（3.8-9.5）内均为磷酰胺浓度的一级。在pH 7.3和37 ℃下的kobsd值如下：PO 3LeuTrp，0.35 h-1; PO 3LeuPhe，0.63 h-1; PO 3LeuPheNH 2，0.73 h-1。kobsd的值在pH 5和pH 8之间没有显著变化，但随着pH的增加而显著降低。在pH约为5以上，PO 3LeuPhe和PO 3LeuPheNH 2的水解与单阴离子物种（NHRPO 3 H）1-的浓度呈正相关，并且计算出各单阴离子物质的一级速率常数的值为0.66 +/-0.03h-1和1.07 +/-0.10h-1。在37摄氏度、pH值4.6和7.7下储存6天后，未发现磷酰胺发生水解，而通过碱水解从磷酰胺中去除L-鼠李糖合成的磷酰胺PO 3LeuTrp在这些条件下迅速水解。PO_3LeuPhe和PO_3LeuPheNH_2在甲醇水溶液中的溶剂分解表明，水解反应是双分子的，是通过溶剂（H_2 O，CH_3OH）对磷的直接进攻进行的。（250字处删节）
The rates of hydrolysis of N-[(alpha-L-rhamnopyranosyloxy)phospho]-L-leucyl-L-tryptophan (phosphoramidon), N alpha-phosphoryl-L-leucyl-L-tryptophan (PO3LeuTrp), N alpha-phosphoryl-L-leucyl-L-phenylalanine (PO3LeuPhe), and N alpha-phosphoryl-L-leucyl-L-phenylalaninamide (PO3LeuPheNH2) were followed by proton nuclear magnetic resonance spectroscopy. The rates of hydrolysis (kobsd) of PO3LeuTrp, PO3LeuPhe, and PO3LeuPheNH2 were all first order in phosphorylamide concentration over the pH range studied (3.8-9.5). The values for kobsd at pH 7.3 and 37 degrees C are as follows: PO3LeuTrp, 0.35 h-1; PO3LeuPhe, 0.63 h-1; PO3LeuPheNH2, 0.73 h-1. The values for kobsd do not significantly change between pH 5 and pH 8 but dramatically decreased with increasing pH. The hydrolysis of PO3LeuPhe and PO3LeuPheNH2 above a pH of approximately 5 was positively correlated with the concentration of monoanionic species (NHRPO3H)1-, and the values for the first-order rate constants for the respective monoanionic species were calculated to be 0.66 +/- 0.03 h-1 and 1.07 +/- 0.10 h-1. Phosphoramidon was not found to hydrolyze after 6 days at 37 degrees C at a pH of 4.6 and 7.7, while the phosphorylamide PO3LeuTrp, synthesized by the removal of L-rhamnose from phosphoramidon by base hydrolysis, was found to rapidly hydrolyze under these conditions. Solvolysis in aqueous methanol of PO3LeuPhe and PO3LeuPheNH2 indicates that the hydrolysis reaction is bimolecular, proceeding by way of direct attack of solvent (H2O, CH3OH) on phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)