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Báo cáo khoa học: Functional site of endogenous phospholipase A2 inhibitor from python serum Phospholipase A2 binding and anti-in¯ammatory activity

The functional site ofÔphospholipase A2 inhibitor from pythonÕ (PIP) was predicted based on the hypothesis of proline brackets. Using di erent sources of secretory phospholipase A2(sPLA2 s) as enzyme, and [ 3 H]arachido-nate-labelledEscherichia colias substrate, short synthetic peptides representing the proposed site were examined for their secretoryphospholipase A2(sPLA2 ) inhibitoryactivity. | Eur. J. Biochem. 269 719-727 2002 FEBS 2002 Functional site of endogenous phospholipase A2 inhibitor from python serum Phospholipase A2 binding and anti-inflammatory activity Maung-Maung Thwin1 Ramapatna L. Satish2 Steven T. F. Chan2 and Ponnampalam Gopalakrishnakone1 Venom and Toxin Research Programme Departments of 1 Anatomy and 2Surgery Faculty of Medicine National University of Singapore Singapore The functional site of phospholipase A2 inhibitor from python PIP was predicted based on the hypothesis of proline brackets. Using different sources of secretory phospholipase A2 sPLA2s as enzyme and 3H arachido-nate-labelled Escherichia coli as substrate short synthetic peptides representing the proposed site were examined for their secretory phospholipase A2 sPLA2 inhibitory activity. A decapeptide P-PB.III proved to be the most potent of the tested peptides in inhibiting sPLA2 enzymatic activity in vitro and exhibited striking anti-inflammatory effects in vivo in a mouse paw oedema model. P-PB.III inhibited the enzymatic activity of class I II and III PLA2s including that of human synovial fluid from arthritis patients. When tested by ELISA biotinylated P-PB.III interacted positively with various PLA2s suggesting that the specific region of PIP corresponding to P-PB.III is likely to be involved in the PLA2-PLI interaction. The effect of P-PB.III on the peritoneal inflammatory response after surgical trauma in rats was also examined. P-PB.III effectively reduced the extent of postsurgical peritoneal adhesions as compared to controls. sPLA2 levels at seventh postoperative day in the peritoneal tissue of P-PB.III-treated rats were also significantly reduced P 0.05 in comparison to those of the untreated controls. The present results shed additional insight on the essential structural elements for PLA2 binding and may be useful as a basis for the design of novel therapeutic agents. Keywords anti-inflammatory peptide phospholipase inhibitor from python PIP protein .