C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 14/73 (2006.01) A61K 38/06 (2006.01) A61K 38/07 (2006.01) A61K 38/08 (2006.01) A61K 38/10 (2006.01) A61K 38/17 (2006.01) C07K 5/093 (2006.01) C07K 5/103 (2006.01) C07K 5/12 (2006.01) C07K 7/06 (2006.01) C07K 7/08 (2006.01) C07K 7/64 (2006.01) A61K 38/00 (2006.01)
Patent
CA 2226017
The application concerns a method of identifying compounds that can be used to inhibit undesired human CD4+ T cell immune responses by identifying compounds that block the interaction of CD4 and MHC, class II, gene products and a method of treatment which comprises administering such an identified compound. The compounds that inhibit undesired human CD4+ T cell immune responses can be used to treat disease such as multiple sclerosis and to prevent graft rejection and graft versus host disease. More specifically, the application concerns compounds having molecular weights between about 1400 and 400 that mimic three portions of the human CD4 lymphocyte cell surface antigen. The portions are residues 29-35, the C-C' loop of the D1 domain; residues 317-323, the C-C' loop of the D4 domain; and residues 346-353, the CDR3 or FG ridge of the D4 domain of the CD4 molecule. Specific examples of such compounds include cyclic peptides and peptidomimetic.
Cette invention concerne un procédé permettant d'identifier des composés pouvant être utilisés pour inhiber les réponses immunitaires indésirables des cellulles CD4¿+? T humaines, au moyen de l'identification de composés qui bloquent l'interaction des produits géniques de classe II de CD4 et MHC, et un procédé de traitement qui consiste à administrer un composé identifié à l'aide dudit procédé. On peut utiliser les composés qui inhibent les réponses immunitaires indésirables des cellules CD4¿+? T humaines pour traiter des maladies telles que la sclérose en plaques et empêcher le rejet de greffe et la réaction du greffon contre l'hôte. Plus spécifiquement cette invention concerne des composés dont les masses molaires se situent entre environ 1400 et 400, ces composés imitant trois parties de l'antigène de surface cellulaire du lymphocyte CD4 humain. Les parties sont les restes 29-35, la boucle C-C' du domaine D1; les restes 317-323, la boucle C-C' du domaine D4; et les restes 346-353, la crête CDR3 ou FG du domaine D4 de la molécule CD4. Des exemples spécifiques de ces composés comprennent des peptides cycliques et des substances peptidomimétiques.
Huang Ziwei
Korngold Robert
Osler Hoskin & Harcourt Llp
Thomas Jefferson University
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