Competitive inhibition of lipolytic enzymes. V. A monolayer study using enantiomeric acylamino analogues of phospholipids as potent competitive inhibitors of porcine pancreatic phospholipase A2 |
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| Institution: | 1. Centre de Biochimie et de Biologie Moléculaire, C.N.R.S., Marseille France;2. Laboratory of Biochemistry, C.B.L.E., Trans 111, Utrecht The Netherlands;3. Groupement de Recherches de Lacq, Groupe Elf Aquitaine, Artix France;1. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan;2. Department of Chemistry, University of Science & Technology, Bannu 28100, KPK, Pakistan;3. Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A2K6, Canada;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India;3. Pharmacology Department, Indian Institute of Chemical Technology, Hyderabad 500 607, India;4. CSIR-Centre for Cellular & Molecular Biology, Hyderabad 500 607, India;1. Beijing Key Laboratory of Multiphase Flow and Heat Transfer for Low Grade Energy Utilization, North China Electric Power University, Beijing 102206, China;2. Key Laboratory of Power Station Energy Transfer Conversion and System (North China Electric Power University), Ministry of Education, Beijing 102206, China;3. Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, School of Energy and Power Engineering, Xi''an Jiaotong University, Xi''an, Shaanxi, 710049, China |
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| Abstract: | For the first time, we have shown that a stereospecific interaction occurs between porcine pancreatic phospholipase A2 and a monomolecular film of amidophospholipid used as inhibitor. Direct binding experiments, using radiolabelled phospholipase A2, showed that 13 times more enzyme was bound to phospholipid films of the l series by comparison with films of the d series. These results were confirmed by indirect binding studies using re-spreading experiments. Kinetic studies of the porcine pancreatic PLA2, using enantiomeric acyl-amino phospholipid analogues, have shown that: (1) inhibitors of the l series are more potent than inhibitors of the d series, (2) inhibitors having a negative charge are more potent than zwitterionic inhibitors, (3) inhibitory power values are greater when evaluated in micellar system than in a the monolayer system, (4) the inhibitory power increases continuously with surface pressure. |
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