摘要:
Heterobifunctional crosslinkers up to about 34 .ANG. in length consisting of a sulfhydryl reactive group linked to a spacer group, which in turn is linked to an activated carboxylate group, that are useful for making efficacious anticancer immunotoxin conjugates as shown preferably by reacting an antibody associated amino group with the activated carboxylate group to form an antibody crosslinker complex and reacting the antibody crosslinker complex with a cytotoxin having a reactive sulfhydryl group with the sulfhydryl reactive group of the crosslinker, and using the conjugates so produced to treat cancer patients.
摘要:
Coupling of biological materials is disclosed via 4-hydroxy-3-nitrobenzene sulfonic acid sodium salt (HNSA) esters. The novel activated esters are structured so as to react at one end with an amine group of a selected biological or non-biological material, thereby releasing the spectroscopically monitorable HNSA dianion, and at the other end with, typically, a sulfhydryl group of a second material which may or may not be biological. The esters provide for a cross-linking reaction that may be easily controlled and monitored.
摘要:
Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要:
A pharmaceutical composition is prepared wherein a biologically active conjugated protein is dissolved in an aqueous carrier medium in the absence of a solubilizing agent. The unconjugated protein, which is not readily water-soluble at pH 6-8 without such solubilizing agent, is covalently conjugated to polyproline via a flexible spacer arm and exhibits substantial biological activity.
摘要:
Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要:
Coupling of biological materials is disclosed via 4-hydroxy-3-nitrobenzene sulfonic acid sodium salt (HNSA) esters. The novel activated esters are structured so as to react at one end with an amine group of a selected biological or non-biological material, thereby releasing the spectroscopically monitorable HNSA dianion, and at the other end with, typically, a sulfhydryl group of a second material which may or may not be biological. The esters provide for a cross-linking reaction that may be easily controlled and monitored.
摘要:
Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## wherein n=1-6R=CH.sub.3, CF.sub.3, --CO.sub.2 R.sup.IV, ##STR2## R.sup.I, R.sup.II =H, F, CH.sub.3, or ##STR3## R.sup.III =H, ##STR4## or tetrazolyl R.sup.IV =H, or alkyland that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.
摘要:
The present invention is a process for preparing a pharmaceutical composition comprising a biologically active conjugated protein. It comprises a polyethylene glycol or a polyoxyethylated polyol conjugated to IL-2. This protein is conjugated to reduce its immunogenicity, and increase it solubility, and increase its circulating in vivo half-life.
摘要:
A coupling agent which is an activated ester such as N-maleimido-6-aminocaproyl-HNSA (mal-sac-HNSA) is formed by reacting 4-hydroxyl-3-nitrobenzene sulfonic acid sodium salt (HNSA) with a carboxylic acid moiety of a compound such as N-maleimido-6-aminocaproic acid. The coupling agent is reacted with an amino group of an amine-containing biological material such as a protein at a pH of about 5.5 to 10.0 and HNSA is released. The released HNSA is spectroscopically measured at a wavelength of from about 350 nm to about 500 nm to precisely monitor and control conjugating of the coupling agent to the biological material. The resulting product is coupled to a sulfhydryl group or other group of another material to provide cross-linking between the two. This enables joining the biological material to one another, to a support matrix, to a label, to a hapten, and to other materials. An immunotoxin for therapeutic use can be prepared by conjugating the coupling agent to an antibody such as a monoclonal antibody with tumor cell specificity and then joining the resultant conjugate to a cytotoxic molecule.
摘要:
Succinylacetone derived or related medicaments and methods of synthesis of the same are shown wherein the medicaments consists of succinylacetonyl-proline-PEG, succinylacetonyl-NH-PEG, or compounds that have the formula: ##STR1## and that have immunosuppressive activity both in vivo and in vitro based on their activities in cellular immunologic assays and adjuvant induced arthritis in rats, respectively.