Peptide macromolecular complexes
First Claim
1. A macromolecular complex which comprises a first and a second peptide macromolecular moiety, joined by a link derived from a linking agent having two or more reactive groups, one of these reactive groups being selected from the group consisting of activated acyl groups, isocyanates, isothiocyanates, iminoethers, iminothioethers and activated halogen atoms attached to aromatic rings and being capable of reacting with one of the macromolecules from which the macromolecular moieties are derived, under conditions where the remaining reactive group or groups which is or are each selected from the group consisting of aziridine rings, aryl azido groups and halogen atoms in an α
- -position relative to a carbonyl group or two carbon atoms removed from a hetero-atom carrying a lone pair of electrons, is or are substantially unreactive.
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Accused Products
Abstract
Macromolecular complexes which comprise a first and a second macromolecular moiety joined by a link derived from a linking agent having two or more reactive groups, one of these reactive groups being an activated acyl group, an isocyanate, an isothiocyanate, an iminoether, an iminothioether or an activated halogen atom attached to an aromatic ring and being capable of reacting with one of the macromolecules from which the macromolecular moieties are derived, under conditions where the remaining reactive group, or groups which is or are each an aziridine ring, an aryl azido group or a halogen atom in an α-position relative to a carbonyl group or two carbon atoms removed from a heteroatom carrying a lone pair of electrons, is or are substantially unreactive.
Methods are provided for making the complexes and so are uses for the complexes. Pharmaceutical formulations containing the complex as are provided.
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Citations
22 Claims
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1. A macromolecular complex which comprises a first and a second peptide macromolecular moiety, joined by a link derived from a linking agent having two or more reactive groups, one of these reactive groups being selected from the group consisting of activated acyl groups, isocyanates, isothiocyanates, iminoethers, iminothioethers and activated halogen atoms attached to aromatic rings and being capable of reacting with one of the macromolecules from which the macromolecular moieties are derived, under conditions where the remaining reactive group or groups which is or are each selected from the group consisting of aziridine rings, aryl azido groups and halogen atoms in an α
- -position relative to a carbonyl group or two carbon atoms removed from a hetero-atom carrying a lone pair of electrons, is or are substantially unreactive.
- View Dependent Claims (2, 3, 20, 21)
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4. A macromolecular complex comprising a first and a second peptide macromolecular moiety, joined by a link derived from a linking agent having two or more reactive groups, in which the link is a radical derived from a compound selected from the group consisting of acyl derivatives of chlorambucil, of 4-(2-chloroethyl)amino benzene butanoic acid, of 2,4-dinitro-5-aziridinylbenzoic acid, and of 5-azido-2,4-dinitrobenzoic acid.
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5. A method of linking peptide macromolecules which comprises:
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(a) reacting a first peptide macromolecule M1 with a linking agent A--L--B in which A is a first reactive group which is selected from the group consisting of activated acyl groups, isocyanates, isothiocyanates, iminoethers, iminothioethers, activated halogen atoms attached to aromatic rings, L is a linking group joining A and B, and B is a second reactive group or further reactive groups which is or are each selected from the group consisting of aziridine rings, aryl azido groups and halogen atoms in an α
-position relative to a carbonyl group or two carbon atoms from a hetero atom carrying a lone pair of electrons, under reaction conditions where the group A is reactive but B is (are) not reactive to give an intermediate M1 --L'"'"'--B in which L'"'"' is the same as L or is derived from L and A(b) reacting the intermediate M1 --L'"'"'--B with a second peptide macromolecule M2 under reaction conditions where the group B is (are) reactive to give a complex M1 --L"--M2 in which L" is the same as L'"'"' or is derived from L'"'"' and B; and (c) isolating the complex produced. - View Dependent Claims (6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 17, 18, 19)
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15. A macromolecular complex which comprises a first antibody macromolecular moiety and a second enzyme macromolecular moiety joined by a link derived from a linking agent having two or more reactive groups, one of these reactive groups being selected from the group consisting of activated acyl groups, isocyanates, isothiocyanates, iminoethers, iminothioethers and activated halogen atoms attached to aromatic rings and being capable of reacting with one of the macromolecules from which the macromolecular moieties are derived, under conditions where the remaining reactive group or groups which is or are each selected from the groups consisting of aziridine rings, aryl azido groups and halogen atoms in an α
- -position relative to a carbonyl group or two carbon atoms removed from a heteroatom carrying a lone pair of electrons, is or are substantially unreactive.
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22. A macromolecular complex which comprises a peptide macromolecular moiety and a phospholipid macromolecular moiety joined by a link derived from a linking agent having two or more reactive groups, one of these reactive groups being selected from the group consisting of activated acyl groups, isocyanates, isothiocyanates, iminoethers, iminothioethers and activated halogen atoms attached to aromatic rings and being capable of reacting with one of the macromolecules from which the macromolecular moieties are derived, under conditions where the remaining reactive group or groups which is or are each selected from the group consisting of aziridine rings, aryl azido groups and halogen atoms in an α
- -position relative to a carbonyl group or two carbon atoms removed from a heteroatom carrying a lone pair of electrons is or are substantially unreactive.
Specification