Composition containing peptide hybrid that includes an aza-beta3-aminoacyl residue, useful particularly as vaccine against disseminated lupus erythematosus, also new antibodies for diagnosis

摘要

Pharmaceutical composition (A), particularly a vaccine, containing a peptide hybrid (PH) analogous to a parent peptide or protein (PP) but including at least one aza-beta 3-aminoacyl residue (X), optionally also a vehicle, is new. Pharmaceutical composition (A), particularly a vaccine, contains a peptide hybrid (PH) analogous to a parent peptide or protein (PP) but including at least one aza-beta 3-aminoacyl residue (X), optionally also a vehicle. (X) has the structure RNH-NR 1-CH 2-CO-; -NH-NR 1-COOH or -NH-NR 1-CO- when present at the N-terminus, C-terminus or internally. R : hydrogen or amino protecting group for amino acids, e.g. Fmoc (fluorenylmethoxycarbonyl), Boc (tert-butoxycarbonyl) or Z (benzyloxycarbonyl); R 1amino acid sidechain. Independent claims are also included for: (1) PH containing at least one (X) and at least one amino acid (aa) from PP, as new compounds; (2) poly- or mono-clonal antibodies (Ab) directed against PH; (3) anti-idiotypic antibodies (AAb) able to form a complex with Ab; (4) complex (C1) between PH and a component of the major histocompatibility complex, optionally also a T-cell receptor (TCR); (5) complex (C2) between PH and TCR; (6) in vitro diagnosis of diseases associated with presence of an exogenous or endogenous protein, using PH to detect specific antibodies or Ab to detect the protein; (7) kit for method (6); (8) preparing aza-beta 3-amino acids (Y); and (9) Fmoc-aza-beta 3-(Gly, Lys, Asp, Met, Arg and Tyr) as new compounds. ACTIVITY : Dermatological; Immunosuppressive; Antiinflammatory. No biological data given. MECHANISM OF ACTION : Vaccine; induction of antibodies and cellular (cytotoxic or auxiliary) responses. Balb/c mice were immunized with the 88-99 epitope of histone H4 (parent peptide), then ( in vitro) T lymphocytes from the mice restimulated and cell proliferation determined from incorporation of tritiated thymidine. The index of stimulation, at 90 MicroM, was about 7 for restimulation with the parent peptide and almost 8 for restimulation with the hybrid peptide NH 2-Tyr-Ala-Leu-Lys-Arg-Glu-Gly-Arg-Thr-Nalpha hLeu-Tyr-Gly (2) where Nalpha hLeu = 3-aza-beta 3-leucine.