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    New peptides as TNF agonists and antagonists - for treatment of neoplastic and auto:immune disease, infection, inflammation and transplant rejection
    11.
    发明专利
    New peptides as TNF agonists and antagonists - for treatment of neoplastic and auto:immune disease, infection, inflammation and transplant rejection 未知

    公开(公告)号：DE4041189A1

    公开(公告)日：1992-06-25

    申请号：DE4041189

    申请日：1990-12-21

    Applicant: BASF AG

    Inventor： BOEHM HANS-JOACHIM DR ,  DAUM LOTHAR DR ,  HAUPT ANDREAS DR ,  PETTIG DAGMAR DR ,  WALKER NIGEL DR ,  MAENNEL DANIELA DR ,  FRANK REINER DR ,  STIEHNER RAINER DR

    IPC: A61K38/00 ,  C07K14/525

    Abstract: Peptides of formula X-Ala-A-B-E-Y (I), derived from tumour necrosis factor (TNF), and their salts with physiologically tolerable acids are new. A is Leu or Phe; B is Leu or Met; X is GNH-CHM-CO, GNH-CHM-CO-W, G-RNH-CHM-CO or G-R-NH-CHM-CO-W; Y is Z, NH-CHQ-COZ, V-NH-CHQ-COZ, NH-CHQ-CO-U-Z or V-NH-CHQ-U-Z; G is H or amino protecting gp.; Z is OH, NH2 or carboxy-protecting gp.; or G and Z together are a covalent bond or CO(CH2)aNH; a is 1-12; R,U,V and W are each peptide chains of 1-4 naturally occurring amino acids; M and Q = H, CHMe2, CHMe-Et, phenyl, CHOH-Me, 3-indolylmethyl, (imidazol-4-yl)methyl or (CH2)bT; b is 1-6; T is H, OH, MeO, MeS, Me2CH, phenyl (opt. 4-OH substd.), SH, NH2, COOH, CONH2, or guanidino; M and Q can together be (CH2)c-S-S-(CH2)-d, (CH2)e-CONH-(CH2)f, or (CH2)e-NH.CO-(-CH2-)-g-NH.CO-(CH2)-f; c and d = 1-4; e and f = 1-6; g = 1-22. (I) are made by standard (chemical or enzymatic) methods of peptide synthesis, initially as linear peptides, opt. followed by an appropriate cyclisation reaction under very dil. conditions. USE/ADVANTAGE - Some (I) are TNF agonists, others are TNF antagonists (these have high affinity for cellular receptors but no activity). Useful for treating neoplastic and autoimmune disorders, and for treating or preventing infections, inflammation and transplant rejection. (I) have a significantly smaller mol. wt. than TNF.

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