Chemically modified a-macroglobulins, methods of making, and met

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

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530402, 530351, C07K14/00

Patent

active

059027878

ABSTRACT:
Chemically modified .alpha.-macroglobulin is conformationally locked by cross-linking .alpha..sub.2 M with a bi-functional peptide crosslinker, and then modified with methylamine, to provide conformational intermediates with limited conformational change. These modified compounds have a high binding affinity for inflammatory cytokines including TNF-.alpha. and IL-1.beta.. When administered in vivo, the modified .alpha..sub.2 M (MAC) protects against development of septic shock, and is an effective treatment aid in treating mammals with established septic shock.

REFERENCES:
Gonias et al. Inactivation of the Plasma Protease Inhibitor J. Macroglobulin by Antitumor Drug Cis-Dichlorodiamne Platinum (11) J. Biol. Chem. vol. 256, No. 23 pp. 12478-12484 1981.
Hayes et al. Modified .zeta..sup.2 -Macroglobulins and Their Use as Scavengers for Cytokine and Growth Factors WO 92/07003 Apr. 30, 1992.
MacPherson et al. Antibody Prodcution for Radioligand Assays. Radionucleotides in Clinical Chemistry, First Edition Little, Brown and Company Boston pp. 77-90 1980.

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