研究C5a反义肽的理论价值和实际意义

Theme significance of antisense peptide of the C5a anaphylatoxin

存在于蛋白质中某些相邻片段的微小表面之间的疏水作用力可以稳定天然蛋白质的构象 ,它也是小肽与蛋白质特异性结合过程中的主要驱动力。在正义DNA链上编码亲水性氨基酸残基的密码子 ,其同一阅读框内所对应的反义DNA链上大多会编码疏水性氨基酸 ,反之亦然。Mekler Biro Blalock模型 (MBB)认为正义 反义肽的相互作用是根据Kyte&Doolittle的疏水 亲水复合指数的疏水性反互补机制 (hydrophobicanticomplementarity)而实现的。在离体和在体实验中 ,都存在有正义 反义多肽发生相互作用的现象 ,如 :一氧化氮合成酶 (nitricoxidesynthase ,NOS)的钙调蛋白结构域的反义肽 ,0 .0 1～ 1 .0mmol L的浓度就能够抑制结构型和诱导型NOS ,其IC(50 )值分别为 98mmol L和 56mmol L ;内皮素受体 (endothelinreceptor ,ETR A)一个片段的反义肽ETR P1 f可抑制内皮素诱导的颈动脉和股动脉血管收缩 ,1 .0 μmol LETR P f反义肽将明显抑制ET 1的功能活性。 0 .2 5μmol L的人C5a反义肽可以保护小鼠免受rh C5a的攻击 ,单独使用rh C5a会使小鼠发生中毒反应 。

The hydrophobic force presents in the microsurface between the proteins could maintain and stabilize their natural conformation. This force is also a principal drive in the specific binding between the peptide and the proteins. The code that codes hydrophobic amino acids on the sense DNA strand could code the hydropathic amino acids on the antisense DNA strand, and vice versa. Mekler and Biro Blalock believed that the interactions between peptide and its antisense peptide is based on the hydrophobic anticomplementarity mechanism of the Kyte & Doolittle's hydropathic /hydrophobic compound index. All experiments in vivo and in vitro , presented the intersections between peptide and its antisense peptide. For instance, the antisense peptide of the calmodulin (CaM) domain in the nitrogen monoxide synthetase (NOS), 0.01- 1.0 mmol/L antisense peptide could inhibited both the constituted type and induced activities of NOS. The IC50 is 98 mmol/L and 56 mmol/L respectively. Another antisense peptide ETR P1/f of the endothelin receptor(ETR A)could inhibit vasoconstriction of carotid artery and femoral artery induced by endothelin. 1.0 μmol/L ETR P/f could inhibit the ET 1' functions. 0.25 μmol/L antisense C5a peptide could prevent the mouse against attack of rh C5a anaphylatoxin.