互补决定区合成肽作为一种微型抗体，在体外可中和1型人类免疫缺陷病毒。
A complementarity-determining region synthetic peptide acts as a miniantibody and neutralizes human immunodeficiency virus type 1 in vitro.
作者信息
Levi M, Sällberg M, Rudén U, Herlyn D, Maruyama H, Wigzell H, Marks J, Wahren B
机构信息
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
出版信息
Proc Natl Acad Sci U S A. 1993 May 15;90(10):4374-8. doi: 10.1073/pnas.90.10.4374.
Abstract
A complementarity-determining region (CDR) of the mouse monoclonal antibody (mAb) F58 was constructed with specificity to a neutralization-inducing region of human immunodeficiency virus type 1 (HIV-1). The mAb has its major reactivity to the amino acid sequence I--GPGRA in the V3 viral envelope region. All CDRs including several framework amino acids were synthesized from the sequence deduced by cloning and sequencing mAb F58 heavy- and light-chain variable domains. Peptides derived from the third heavy-chain domain (CDR-H3) alone or in combination with the other CDR sequences competed with F58 mAb for the V3 region. The CDR-H3 peptide was chemically modified by cyclization and then inhibited HIV-1 replication as well as syncytium formation by infected cells. Both the homologous IIIB viral strain to which the F58 mAb was induced and the heterologous SF2 strain were inhibited. This synthetic peptide had unexpectedly potent antiviral activity and may be a potential tool for treatment of HIV-infected persons.
摘要
构建了小鼠单克隆抗体（mAb）F58的互补决定区（CDR），使其对1型人类免疫缺陷病毒（HIV-1）的中和诱导区具有特异性。该单克隆抗体主要与V3病毒包膜区域的氨基酸序列I--GPGRA发生反应。所有的CDR，包括几个框架氨基酸，都是根据通过克隆和测序mAb F58重链和轻链可变结构域推导出来的序列合成的。单独来源于第三重链结构域（CDR-H3）或与其他CDR序列组合的肽与F58单克隆抗体竞争V3区域。CDR-H3肽通过环化进行化学修饰，然后抑制HIV-1复制以及感染细胞的合胞体形成。F58单克隆抗体所针对的同源IIIB病毒株和异源SF2病毒株均受到抑制。这种合成肽具有出乎意料的强效抗病毒活性，可能是治疗HIV感染者的潜在工具。
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