核酮糖-1,5-二磷酸羧化酶/加氧酶抑制蛋白作为δ阿片肽的构效关系

Structure-activity relationship of rubiscolins as delta opioid peptides.

作者信息

Yang Shuzhang, Sonoda Soushi, Chen Liping, Yoshikawa Masaaki

机构信息

Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Japan.

出版信息

Peptides. 2003 Apr;24(4):503-8. doi: 10.1016/s0196-9781(03)00117-7.

DOI:10.1016/s0196-9781(03)00117-7

PMID:12860192

Abstract

To study the structure-activity relationship of rubiscolins (YPLDLF and YPLDL), delta opioid peptides derived from the spinach Rubisco, we substituted the amino acid residues and evaluated their activities by mouse vas deferens (MVD) and guinea pig ileum (GPI) assays as well as receptor affinity. Replacement of Leu(3) with Ile and Met in rubiscolin-6 potentiated the delta opioid activity by about four times in MVD assay. Asp(4) cannot be replaced by Ala, Glu or His. The original Leu(5) was optimal, while substitution of Phe(6) with Val potentiated its delta opioid activity by more than 10 times. The most potent derivative we obtained was YPMDLV, which was nearly 20 times more potent than rubiscolin-6 in MVD assay. The derivatives thus obtained showed higher delta receptor affinity and more potent antinociceptive activity than rubiscolins.

摘要

为了研究源自菠菜核酮糖-1,5-二磷酸羧化酶/加氧酶的δ阿片肽rubiscolins（YPLDLF和YPLDL）的构效关系，我们对氨基酸残基进行了替换，并通过小鼠输精管（MVD）和豚鼠回肠（GPI）试验以及受体亲和力评估了它们的活性。在rubiscolin-6中用异亮氨酸和甲硫氨酸替换亮氨酸（3），在MVD试验中使δ阿片活性增强了约四倍。天冬氨酸（4）不能被丙氨酸、谷氨酸或组氨酸取代。原来的亮氨酸（5）是最佳的，而用缬氨酸替换苯丙氨酸（6）使其δ阿片活性增强了10倍以上。我们获得的最有效的衍生物是YPMDLV，在MVD试验中其效力比rubiscolin-6强近20倍。由此获得的衍生物显示出比rubiscolins更高的δ受体亲和力和更强的抗伤害感受活性。