Inhibition of microbial lipases with stereoisomeric triradylglycerol analog phosphonates

被引:29
作者
Stadler, P
Zandonella, G
Haalck, L
Spener, F
Hermetter, A
Paltauf, F
机构
[1] GRAZ UNIV TECHNOL, INST BIOCHEM & LEBENSMITTELCHEM, SPEZIAL FORSCH BEREICH BIOKATALYSE, A-8010 GRAZ, AUSTRIA
[2] INST CHEMO & BIOSENSOR, MUNSTER, GERMANY
[3] UNIV MUNSTER, INST BIOCHEM, D-4400 MUNSTER, GERMANY
来源
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM | 1996年 / 1304卷 / 03期
关键词
microbial lipase; inhibition; phosphonate; triacylglycerol analog; fluorescent pyrene lipid; stereoselectivity;
D O I
10.1016/S0005-2760(96)00123-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
1,2(2,3)-Diradylglycero O-(p-nitrophenyl) n-hexylphosphonates were synthesized, with the diradylglycerol moiety being di-O-octylglycerol, 1-O-hexadecyl-2-O-pyrenedecanylglycerol, or 1-O-octyl-2-oleoyl-glycerol, and tested for their ability to inactivate lipases from Chromobacterium viscosum (CVL) and Rhizopus oryzae (ROL). The experimental data indicate the formation of stable, covalent 1:1 enzyme-inhibitor adducts with the di-O-alkylglycero phosphonates. The differences in reactivity of diastereomeric phosphonates with opposite configuration at the glycerol backbone was less expressed with both enzymes tested as compared to the influence of the stereochemistry at the phosphorus. Both lipases exhibited the same preference for the chirality at the phosphorus that was independent from the absolute configuration at the glycerol backbone. However, with CVL and ROL the inhibitors with the active site serine-directed phosphonate linked at position sn-1 of the glycerol moiety reacted significantly faster than the corresponding sn-3 analogs, reflecting the sn-1 stereopreference of the enzymes towards triacylglycerol analogs with a sn-2 O-alkyl substituent. In contrast, the phosphonates based on the 1-O-octyl-2-oleoylglycerol did not significantly inactivate CVL. Unexpectedly, these substances were hydrolyzed in the presence of lipase.
引用
收藏
页码:229 / 244
页数:16
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