| 摘要 |
<p>Peptide (I) of 5-40 amino acids (aa) derived from a cytokine in which at least one aa has at least one of its atoms spaced a distance (d), evaluated from structural data, less than 5 Å from an atom of the corresponding cytokine receptor is new. Excluded are peptides from between the 2nd and 3rd Cys of RANTES and from residues 123-140 of interferon alpha . Independent claims are also included for: (1) derivatives (Ia) of (I) produced by deletion, substitution, addition, cyclization, stereochemical modification (use of D amino acids) or functionalization (e.g. acylation) of one or more aa; and (2) immunogenic compound that comprises (I) or (Ia) provided that is does not contain other cytokine epitopes and can generate antibodies that recognize the native cytokine. ACTIVITY : Immunosuppressive; Neuroprotective; Antirheumatic; Antiarthritic; Antipsoriatic; Antidiabetic; Dermatological; Antiinflammatory; Antiallergic; Antiasthmatic; Cytostatic; Anti-HIV. MECHANISM OF ACTION : Vaccine. The peptide Leu-His-Leu-Gln-Gly-Gln-Asp-Met-Glu-Gln-Gln (residues 123-132 of human interleukin-1 beta ) was attached to Lys at the N-terminus then coupled to keyhole limpet hemocyanin. The immunogen was administered (with adjuvants) to mice: 40 Microg on day 0 and 20 Microg on each of days 21 and 40. On day 60 antibodies against human IL-1 beta were measured; the enzyme-linked immunosorbent assay titer was 1.15, compared with 0.08 in unvaccinated controls. The induced antibodies were neutralizing.</p> |
