Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Sign In to gain access to subscriptions and/or personal tools.
Journal of Biomolecular Screening
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by He Xiao
Right arrow Articles by Yan Li
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by He Xiao,
Right arrow Articles by Yan Li,
Right arrowPubmed/NCBI databases
*Substance via MeSH
Hazardous Substances DB
*THIOPHENE
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

A5, a New Small-Molecule Inhibitor of CD4 D1 Obtained from a Computer-Aided Screening Method, Contributes to the Inhibition of CD4+ T-cell Function

He Xiao

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Jian-Nan Feng

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Zu-Yin Yu

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Lei Zhang

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Ming Yu

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Xin-Hua He

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Song Li

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Bei-Fen Shen

Department of Molecular Immunology, Institute of Basic Medical Sciences, Beijing, China, Department of Pathophysiology, Institute of Radiation Medicine, Beijing, China, Department of Molecular Drug Design, Institute of Pharmacology and Toxicology Sciences, Beijing, China

Yan Li

Department of Molecular Immunology Institute of Basic Medical Sciences Beijing, 100850 China, liyan62033{at}yahoo.com.cn

In this study, the authors apply a computer-based strategy to screen thousands of small-molecule, nonpeptidic organic compounds in the Available Chemicals Directory database and to select a series of potential candidates as ligands of the proposed CD4 D1 surface pocket. Then, several cell-based models are used to determine the actual biological functions of these compounds. A small molecule designated A5 (N-((pyridine-4-yl)methylene)thiophene-2-carbohydrazide) was obtained by a virtual screening followed by 3 cell-based functional assays. The results show that A5 could specifically block the CD4—major histocompatibility complex II binding in a rosetting assay, inhibit the mixed lymphocyte reaction—induced T-cell proliferation in a concentration-dependent manner, and reduce the PMA plus ionomycin—stimulated interleukin-2 secretion from peripheral blood mononuclear cells. (Journal of Biomolecular Screening 2007:800-808)

Key Words: CD4—MHC II interaction • computer-aided screening • novel CD4 D1 inhibitor • cell-based functional assays

References

  • Janin J., Chothia C.: The structure of protein-protein recognition sites . J Biol Chem 1990;265: 16027-16030 .[Free Full Text]
  • Davies DR, Padlan EA, Sheriff S.: Antibody-antigen complexes . Annu Rev Biochem 1990;59: 439-473 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Littman DR: The structure of the CD4 and CD8 genes . Annu Rev Immunol 1987;5: 561-584 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Wang J., Yan Y., Garrett Tpj, Liu J., Rodgers DW, Garlick RL, et al: Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains . Nature 1990;348: 411-418 .[CrossRef][Medline] [Order article via Infotrieve]
  • Wu H., Kwong PD, Hendrickson WA: Dimeric association and segmental variability in the structure of human CD4 . Nature (London) 1997;387: 527-530 .[CrossRef][Medline] [Order article via Infotrieve]
  • Moebius U., Clayton LK, Abraham S., Diener A., Yunis JJ, Harrison SC: Human immunodeficiency virus gp120 binding C'C'' ridge of CD4 domain 1 is also involved in interaction with class II major histocompatibility complex molecules. Proc Natl Acad Sci U S A 1992;89:12008-12012.
  • Moebius U., Pallai P., Harrison SC, Reinherz EL: Delineation of an extended surface contact area on human CD4 involved in class II major histocompatibility complex binding . Proc Natl Acad Sci U S A 1993;90: 8259-8263 .[Abstract/Free Full Text]
  • Leahy DJ: A structural view of CD4 and CD8 . FASEB J 1995;9: 17-25 .[Abstract]
  • Li S., Gao J., Satoh T., Friedman T., Edling A., Koch U., et al: A computer screening approach to immunoglobulin superfamily structures and interactions: discovery of small non-peptidic CD4 inhibitors as novel immunotherapeutics . Proc Natl Acad Sci U S A 1997;94: 73-78 .[Abstract/Free Full Text]
  • Jameson BA, McDonnell JM, Marini JC, Korngold R.: A rationally designed CD4 analogue inhibits experimental allergic encephalomyelitis . Nature 1994;368: 744-746 .[CrossRef][Medline] [Order article via Infotrieve]
  • Friedman TM, Reddy AP, Wassell R., Jameson BA, Korngold R.: Identification of a human CD4-CDR3-like surface involved in CD4+ T cell function . J Biol Chem 1996;271: 22635-22640 .[Abstract/Free Full Text]
  • Satoh T., Aramini JM, Li S., Friedman TM, Gao J., Edling A., et al: Bioactive peptide design based on protein surface epitopes: a cyclic heptapeptide mimics CD4 domain 1 CC' loop and inhibits CD4 biological function . J Biol Chem 1997;272: 12175-12180 .[Abstract/Free Full Text]
  • Meng EC, Shoichet BK, Kuntz ID: Automated docking with grid-based energy evaluation . J Comput Chem 1992;13: 505-524 .[CrossRef][Web of Science]
  • Ring CS, Sun E., McKerrow JH, Lee GK, Rosenthal PJ, Kuntz ID, et al: Structure-based inhibitor design by using protein models for the development of antiparasitic agents . Proc Natl Acad Sci U S A 1993;90: 3583-3587 .[Abstract/Free Full Text]
  • Xiao H., Feng JN, He XH, Zhang H., Zhang JR, Zhang L., et al: Potent inhibition of the CD4-dependent T cell response by J2, a novel nonpeptide organic ligand of CD4 D1 . Mol Immunol 2007;44: 784-795 .[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Xiao H., Zhang H., Yu ZY, Zhang L., Yu M., Huang YF, et al: J2 prolongs the corneal allograft survival through inhibition of the CD4+ T cell-mediated response in vivo . Transpl Immunol. Forthcoming.

This version was published on September 1, 2007

Journal of Biomolecular Screening, Vol. 12, No. 6, 800-808 (2007)
DOI: 10.1177/1087057107305505
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?



This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via Google Scholar
Right arrow Citing Articles via Scopus
Google Scholar
Right arrow Articles by He Xiao
Right arrow Articles by Yan Li
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by He Xiao,
Right arrow Articles by Yan Li,
Right arrowPubmed/NCBI databases
*Substance via MeSH
Hazardous Substances DB
*THIOPHENE
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?