Antibodies to inhibin and conjugates produced therefrom

Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...

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530388, 530389, 525 541, A61K 3514, C07G 700

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active

048640190

ABSTRACT:
A 32,000-Dalton protein with inhibin activity is isolated from porcine follicular fluid which is composed of two chains having molecular weights of about 18,000 and about 14,000 Daltons, which are bound together by disulfide bonding. Microsequencing revealed the NH.sub.2 -terminal portion of the 18 kD chain to be Ser-Thr-Ala-Pro-Leu-Pro-Trp-Pro-Trp-Ser-Pro-Ala-Ala-Leu-Arg-Leu-Leu-Gln-Ar g- Pro-Pro-Glu-Glu-Pro-Ala-Val and of the 14 kD chain to be Gly-Leu-Glu-Cys with the next 21 residues believed to be Asp-Gly-Ser-His-Asn-Leu-Asp-Ser-Arg-Gln-Gln-Phe-Phe-Ile-Asp-Phe-Arg-Leu-Il e-G y-Trp. This 32 kD protein specifically inhibits basal secretion of FSH, but not of LH. Antibodies raised against a synthetic replicate of the N-terminal six residues of the 18 kD chain are effective to reduce the activity of highly purified 32 kD inhibin and may be administered to mammalian animals for the purpose of neutralizing endogenous inhibin and thereby increasing gonadotropin secretion. The antibodies are also useful in immunoassays to determine inhibin levels in mammalian fluids. To generate the antibodies, short chain peptides are synthesized which mimic portions of natural mammalian inhibin protein chains, the synthetic peptides are conjugated to large carrier molecules and the conjugates are used as inoculum to induce a mammalian immune system to produce inhibin-reactive antibodies.

REFERENCES:
patent: 4474757 (1984-10-01), Arnon et al.
patent: 4493795 (1985-01-01), Nestor, Jr. et al.
patent: 4740587 (1988-04-01), Ling et al.
D. M. Robertson et al., "Isolation of Inhibin from Bovine Follicular Fluid", B.B.R.C., 126, No. 1, 220-226 (1985).
Jean Rivier et al., "Purification and Partial Characterization of Inhibin from Porcine Follicular Fluid", B.B.R.C., 133, No. 1, 120-127 (1985).

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