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. 1989 Jul;86(14):5537–5541. doi: 10.1073/pnas.86.14.5537

Development of biologically active peptides based on antibody structure.

W V Williams 1, D A Moss 1, T Kieber-Emmons 1, J A Cohen 1, J N Myers 1, D B Weiner 1, M I Greene 1
PMCID: PMC297658  PMID: 2501789

Abstract

Antibody molecules are composed of several functional domains, including a variable domain that contacts antigen and a constant domain. The hypervariable regions of antibody molecules play an integral role in determining their specificity. However, the delineation of specific residues most critical in binding is difficult. We have been studying a monoclonal antibody (87.92.6) that binds to the reovirus type 3 receptor on a number of cell types, down-modulates the receptor, and inhibits DNA synthesis in the cells. We have shown that a peptide derived from the second complementarity-determining region of the monoclonal antibody 87.92.6 light-chain variable region can reproduce both of these effects. We were also able to demonstrate specific amino acid residues and structural features involved in producing these effects. The study of antibody structure, coupled with molecular synthetic techniques, can lead to the development of biologically active substances with potential clinical use.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bassel-Duby R., Jayasuriya A., Chatterjee D., Sonenberg N., Maizel J. V., Jr, Fields B. N. Sequence of reovirus haemagglutinin predicts a coiled-coil structure. 1985 May 30-Jun 5Nature. 315(6018):421–423. doi: 10.1038/315421a0. [DOI] [PubMed] [Google Scholar]
  2. Bruck C., Co M. S., Slaoui M., Gaulton G. N., Smith T., Fields B. N., Mullins J. I., Greene M. I. Nucleic acid sequence of an internal image-bearing monoclonal anti-idiotype and its comparison to the sequence of the external antigen. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6578–6582. doi: 10.1073/pnas.83.17.6578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burstin S. J., Spriggs D. R., Fields B. N. Evidence for functional domains on the reovirus type 3 hemagglutinin. Virology. 1982 Feb;117(1):146–155. doi: 10.1016/0042-6822(82)90514-1. [DOI] [PubMed] [Google Scholar]
  4. Cashdollar L. W., Chmelo R. A., Wiener J. R., Joklik W. K. Sequences of the S1 genes of the three serotypes of reovirus. Proc Natl Acad Sci U S A. 1985 Jan;82(1):24–28. doi: 10.1073/pnas.82.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Co M. S., Gaulton G. N., Fields B. N., Greene M. I. Isolation and biochemical characterization of the mammalian reovirus type 3 cell-surface receptor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1494–1498. doi: 10.1073/pnas.82.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Co M. S., Gaulton G. N., Fields B. N., Greene M. I. Isolation and biochemical characterization of the mammalian reovirus type 3 cell-surface receptor. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1494–1498. doi: 10.1073/pnas.82.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Epstein R. L., Powers M. L., Rogart R. B., Weiner H. L. Binding of 125I-labeled reovirus to cell surface receptors. Virology. 1984 Feb;133(1):46–55. doi: 10.1016/0042-6822(84)90424-0. [DOI] [PubMed] [Google Scholar]
  8. Gaulton G. N., Greene M. I. Inhibition of cellular DNA synthesis by reovirus occurs through a receptor-linked signaling pathway that is mimicked by antiidiotypic, antireceptor antibody. J Exp Med. 1989 Jan 1;169(1):197–211. doi: 10.1084/jem.169.1.197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gaulton G., Co M. S., Greene M. I. Anti-idiotypic antibody identifies the cellular receptor of reovirus type 3. J Cell Biochem. 1985;28(1):69–78. doi: 10.1002/jcb.240280110. [DOI] [PubMed] [Google Scholar]
  10. Gentsch J. R., Pacitti A. F. Effect of neuraminidase treatment of cells and effect of soluble glycoproteins on type 3 reovirus attachment to murine L cells. J Virol. 1985 Nov;56(2):356–364. doi: 10.1128/jvi.56.2.356-364.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hand R., Tamm I. Reovirus: effect of noninfective viral components on cellular deoxyribonucleic acid synthesis. J Virol. 1973 Feb;11(2):223–231. doi: 10.1128/jvi.11.2.223-231.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kauffman R. S., Noseworthy J. H., Nepom J. T., Finberg R., Fields B. N., Greene M. I. Cell receptors for the mammalian reovirus. II. Monoclonal anti-idiotypic antibody blocks viral binding to cells. J Immunol. 1983 Nov;131(5):2539–2541. [PubMed] [Google Scholar]
  13. Lee P. W., Hayes E. C., Joklik W. K. Protein sigma 1 is the reovirus cell attachment protein. Virology. 1981 Jan 15;108(1):156–163. doi: 10.1016/0042-6822(81)90535-3. [DOI] [PubMed] [Google Scholar]
  14. Martin P. J., Hansen J. A., Anasetti C., Zutter M., Durnam D., Storb R., Thomas E. D. Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies. Am J Kidney Dis. 1988 Feb;11(2):149–152. doi: 10.1016/s0272-6386(88)80201-4. [DOI] [PubMed] [Google Scholar]
  15. Masri S. A., Nagata L., Mah D. C., Lee P. W. Functional expression in Escherichia coli of cloned reovirus S1 gene encoding the viral cell attachment protein sigma 1. Virology. 1986 Feb;149(1):83–90. doi: 10.1016/0042-6822(86)90089-9. [DOI] [PubMed] [Google Scholar]
  16. Nagata L., Masri S. A., Mah D. C., Lee P. W. Molecular cloning and sequencing of the reovirus (serotype 3) S1 gene which encodes the viral cell attachment protein sigma 1. Nucleic Acids Res. 1984 Nov 26;12(22):8699–8710. doi: 10.1093/nar/12.22.8699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nepom J. T., Tardieu M., Epstein R. L., Noseworthy J. H., Weiner H. L., Gentsch J., Fields B. N., Greene M. I. Virus-binding receptors: similarities to immune receptors as determined by anti-idiotypic antibodies. Surv Immunol Res. 1982;1(3):255–261. doi: 10.1007/BF02918466. [DOI] [PubMed] [Google Scholar]
  18. Noseworthy J. H., Fields B. N., Dichter M. A., Sobotka C., Pizer E., Perry L. L., Nepom J. T., Greene M. I. Cell receptors for the mammalian reovirus. I. Syngeneic monoclonal anti-idiotypic antibody identifies a cell surface receptor for reovirus. J Immunol. 1983 Nov;131(5):2533–2538. [PubMed] [Google Scholar]
  19. Pacitti A. F., Gentsch J. R. Inhibition of reovirus type 3 binding to host cells by sialylated glycoproteins is mediated through the viral attachment protein. J Virol. 1987 May;61(5):1407–1415. doi: 10.1128/jvi.61.5.1407-1415.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sharpe A. H., Fields B. N. Reovirus inhibition of cellular DNA synthesis: role of the S1 gene. J Virol. 1981 Apr;38(1):389–392. doi: 10.1128/jvi.38.1.389-392.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spriggs D. R., Kaye K., Fields B. N. Topological analysis of the reovirus type 3 hemagglutinin. Virology. 1983 May;127(1):220–224. doi: 10.1016/0042-6822(83)90385-9. [DOI] [PubMed] [Google Scholar]
  22. Taub R., Gould R. J., Garsky V. M., Ciccarone T. M., Hoxie J., Friedman P. A., Shattil S. J. A monoclonal antibody against the platelet fibrinogen receptor contains a sequence that mimics a receptor recognition domain in fibrinogen. J Biol Chem. 1989 Jan 5;264(1):259–265. [PubMed] [Google Scholar]
  23. Weiner H. L., Drayna D., Averill D. R., Jr, Fields B. N. Molecular basis of reovirus virulence: role of the S1 gene. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5744–5748. doi: 10.1073/pnas.74.12.5744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Weis W., Brown J. H., Cusack S., Paulson J. C., Skehel J. J., Wiley D. C. Structure of the influenza virus haemagglutinin complexed with its receptor, sialic acid. Nature. 1988 Jun 2;333(6172):426–431. doi: 10.1038/333426a0. [DOI] [PubMed] [Google Scholar]
  25. Williams W. V., Guy H. R., Rubin D. H., Robey F., Myers J. N., Kieber-Emmons T., Weiner D. B., Greene M. I. Sequences of the cell-attachment sites of reovirus type 3 and its anti-idiotypic/antireceptor antibody: modeling of their three-dimensional structures. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6488–6492. doi: 10.1073/pnas.85.17.6488. [DOI] [PMC free article] [PubMed] [Google Scholar]

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