BINDING-AFFINITY AND PHYSIOLOGICAL-ACTIVITY OF SOME HVFLRFAMIDE ANALOGS ON THE OVIDUCTS OF THE LOCUST, LOCUSTA-MIGRATORIA
BINDING-AFFINITY AND PHYSIOLOGICAL-ACTIVITY OF SOME HVFLRFAMIDE ANALOGS ON THE OVIDUCTS OF THE LOCUST, LOCUSTA-MIGRATORIA
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DOI：
10.1016/0167-0115(95)00047-f
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发表时间：
1995-06-27
影响因子：
--
通讯作者：
LANGE, AB
中科院分区：
文献类型：
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作者：
WANG, ZX;ORCHARD, I;LANGE, AB
SchistoFLRFamide (PDVDIIVFLRFamide) 是一种昆虫神经肽，可抑制蝗虫输卵管的自发收缩和诱导收缩。抑制活性核心位于序列 HVFLRFamide 内，而结合核心位于序列 VFLRFamide 内。后一种肽表现出活性逆转，具有较小的刺激活性。采用生物测定和受体结合测定来确定HVFLRFamide类似物对飞蝗输卵管的结合亲和力和生物活性之间的关系。 VFLRFamide序列中的每个氨基酸被结构相似或不相似的氨基酸取代以产生一组HVFLRFamide类似物。测试了这些类似物与蝗虫输卵管膜中受体的结合亲和力以及它们对分离的蝗虫输卵管收缩的生物效应。结果表明：（1）1位有His残基，没有实现活性逆转，类似物要么是抑制性的，要么不具有生物活性； (2) C 端 RFamide 基团对于类似物的结合亲和力和生物活性至关重要，(3) 用结构相似的氨基酸 Lys(5) 或 Tyr(6) 取代 Arg(5) 或 Phe(6) 可产生两种高亲和力拮抗剂，而用 Leu(2) 或 Ala(2) 取代 Val(2) 可产生高亲和力激动剂。
SchistoFLRFamide (PDVDIIVFLRFamide) is an insect neuropeptide which inhibits spontaneous and induced contractions of locust oviduct. The active core for inhibition lies within the sequence HVFLRFamide, whereas the core for binding lies within the sequence VFLRFamide. This latter peptide shows activity reversal, possessing minor stimulatory activity. The bioassay and receptor binding assay were employed to define the relationship between the binding affinity and biological activity of HVFLRFamide analogues on the oviduct of Locusta migratoria. Each amino acid in the sequence VFLRFamide was substituted with a structurally similar or dissimilar amino acid to yield a group of HVFLRFamide analogues. These analogues were tested for their binding affinity to receptors in locust oviduct membrane and for their biological effects on contractions of the isolated locust oviduct. The results indicate that (1) with the His residue in position 1, no activity reversal is achieved, the analogues are either inhibitory or possess no biological activity; (2) the C-terminal RFamide group is critical for binding affinity and biological activity of the analogues and (3) substitution of Arg(5) or Phe(6) with structurally similar amino acids Lys(5) or Tyr(6) results in two high-affinity antagonists, while substitution of Val(2) with Leu(2) or Ala(2) results in high-affinity agonists.