Synthetic immunogens. Part IV: Conformational studies on gastrin conjugates with the human immunoglobulin G1 hinge peptide 225-232/225'-232'.
Hybrids of the double-chain bis-cystinyl fragment 225-232/225'-232' of human immunoglobulin G1 (IgG1) with the human little-gastrin sequence 2-17 were found to induce in animals a strong antigastrin humoral immune response with antibody titers comparable to those raised with conventional gastrin/carrier-protein conjugates. The observed gastrin receptor-like specificity of the polyclonal antibodies led to the assumption that the gastrin component of the hybrids is still capable of folding into its preferred bioactive structure and thus to express a similar conformational epitope in the dynamic process of recognition by the B-cell receptors. CD measurements on these hybrid compounds in aqueous and aqueous organic media confirmed the free conformational space for the antigenic gastrin moiety, which is essentially randomly coiled in aqueous solution but retains its ability to fold into the gastrin-specific ordered structure in aqueous organic media as used to mimic the water-limited environment of peptides while interacting with target cells at receptor level. The absence of reciprocal conformational restriction in such hybrid molecules suggests that a compact, rigid heterodetic cyclic structure as the hinge peptide is well suited for the multiple attachment of antigenic sequences in view of the preparation of fully synthetic immunogens.
Moroder
L
L
Max-Planck Institut für Biochemie, Abteilung Peptidchemie, Martinsried, Federal Republic of Germany.
Bali
J P
JP
Kobayashi
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002942:Circular Dichroism; D005755:Gastrins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry; D011487:Protein Conformation
D000906:Antibodies; D005755:Gastrins; D007074:Immunoglobulin G; D009842:Oligopeptides