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细胞因子白细胞介素-1的互补(反义)肽微型受体抑制剂的机制研究

Mechanistic investigation into complementary (antisense) peptide mini-receptor inhibitors of cytokine interleukin-1.

作者信息

Hea Jonathan R, Bino Sylvia, Roberts Gareth W, Raynes John G, Miller Andrew D

机构信息

Imperial College Genetic Therapies Centre, Department of Chemistry, Flowers Building, Armstrong Road Imperial College of Science, Technology and Medicine South Kensington, London, SW72AZ, UK.

出版信息

Chembiochem. 2002 Jan 4;3(1):76-85. doi: 10.1002/1439-7633(20020104)3:1<76::AID-CBIC76>3.0.CO;2-N.

DOI:10.1002/1439-7633(20020104)3:1<76::AID-CBIC76>3.0.CO;2-N
PMID:17590957
Abstract

Sense peptides are coded for by the nucleotide sequence (read 5'-->3') of the sense (positive) strand of DNA. Conversely, a complementary peptide is coded for by the nucleotide sequence (read 5'-->3') of the complementary or antisense (negative) strand of DNA. In many instances, sense and corresponding complementary peptides have been observed to interact specifically. In order to study this process in more detail, longer, shorter and mutant variants of our original complementary peptide, VITFFSL, were synthesised and analysed for binding to and inhibition of cytokine human interleukin-1beta (IL- 1beta) in vitro. The behaviour of all peptides studied is discussed in terms of the Mekler- dlis (M-1) pair theory, a theory that accounts for specific sense-complementary peptide interactions in terms of through-space interactions between corresponding pairs of amino acid residues (M-1 pairs)] specified by the genetic code and its complement.

摘要

有义肽由DNA有义(正)链的核苷酸序列(从5'→3'读取)编码。相反,互补肽由DNA互补或反义(负)链的核苷酸序列(从5'→3'读取)编码。在许多情况下,已观察到有义肽和相应的互补肽会特异性相互作用。为了更详细地研究这一过程,我们合成了原始互补肽VITFFSL的更长、更短和突变变体,并在体外分析它们与细胞因子人白细胞介素-1β(IL-1β)的结合及抑制作用。根据梅克勒-迪利斯(M-1)对理论讨论了所有研究肽的行为,该理论根据遗传密码及其互补序列指定的相应氨基酸残基对(M-1对)之间的空间相互作用来解释特定的有义-互补肽相互作用。

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