Polypeptide derivatives
OwnerRainer Albert, Wilfried Bauer +1inventors
InventorsRainer Albert, Wilfried Bauer, Janos Pless
Life of this patent
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Abstract
A biologically active peptide selected from growth factors, peptide hormones, interferons and cytokines and analogues and derivatives thereof, and bearing at least one chelating group linked to an amino group of said peptide, the chelating group being capable of complexing a detectable element and such amino group having no significant binding affinity to target receptors, are complexed with a detectable element and are useful as a pharmaceutical, e.g. a radiopharmaceutical for in vivo imaging of target tissues or for therapy.
Claims27
A biologically active peptide selected from the group consisting of growth factors, insulin, LHRH, gastrin, gastrin releasing peptide, thyrotropin releasing hormone, thyroid stimulating hormone, prolactin, vasoactive intestinal peptide, angiotensin, interferons, IL-1, IL-4 and IL-6, and analogues or derivatives thereof and bearing at least one chelating group linked to an amino group of said peptide, the chelating group being capable of complexing a detectable element and such amino group having no significant binding affinity to target receptors.
A biologically active peptide selected from the group consisting of epidermal growth factor, LHRH, LHRH agonists, LHRH antagonists, bombesin and bombesin antagonists and analogues and derivatives thereof, and bearing at least one chelating group linked to an amino group of said peptide, the chelating group being capable of complexing a detectable element and such amino group having no significant binding affinity to target receptors.
A physiologically peptide selected from the group consisting of growth factors, peptide hormones, interferons and cytokines and analogues or derivatives thereof, and bearing a chelating group linked either directly or indirectly by means of a divalent bridging group to an amino group of said peptide, the chelating group being derived from N′-p-isothiocyanatobenzyl-diethylene triamine-N,N,N″,N″-tetraacetic acid, N′-p-isothiocyanatophenethyl-diethylene triamine-N,N,N″,N″-tetraacetic acid, N-{2-[bis(carboxymethyl)amino]ethyl}-N′-{2-[bis(carboxymethyl)amino]-2-(p-isothiocyanatobenzyl)-ethyl}-glycine, DOTA, C-functionalised tetraazacyclododecane-tetraacetic acids, C-functionalised tetraazacyclotetradecane-tetraacetic acids, C-functionalised triazacyclododecane triacetic acids, C-functionalised triazacyclononane triacetic acids and a compound of formula V
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- wherein
- each of R24, R25, R26, R27, R28 and R29 independently is hydrogen or C1-4alkyl,
- m′ is 2 or 3, and
- X2 is p-isothiocyanato-benzyl or -phenethyl,
- the chelating group being capable of complexing a detectable element and said amino group having no significant binding affinity to target receptors.
A peptide which is DTPA-O-Ala-mEGF, [DTPA-β-Ala-Trp14]-tetragastrin, acetyl-DPhe(pCl)-DPhe(pCl)-DTrp-Ser-Tyr-DLys(DTPA)-Leu-Arg-Pro-DAla-NH2, DTPA-DNal-(2)1-DPhe(p-Cl)-DTrp-Ser-Tyr-DLys(CH2—CHOH—CH2OH)-Leu-Lys(CH2—CHOH—CH2OH)-Pro-DAla-NH2 and acetyl-His-Trp-Ala-Val-DAla-Lys(β-Ala-DTPA)-Leu-OEt.
A compound of formula XI
- A-Z-R-Z2-X7 (XI)
- wherein
- A is a chelating group,
- Z is a divalent group derived from a functional moiety capable of covalently reacting with a chelating agent,
- R is C1-11alkylene, hydroxy substituted C2-11alkylene, C2-11alkenylene,
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- cyclohexylene, substituted cyclohexylene, or a radical of formula (α2)
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- wherein each of n and m independently is 0, 1, 2 or 3,
- the ring A is substituted or unsubstituted, and
- R5 is a residue as attached in Cα of a natural or synthetic α-amino acid, and
- Z2 is COOH or a functional group of a carboxy function,
- or a compound of formula XII
- A-Z′1l-CO—X7 (XII)
- wherein
- A is as defined above,
- Z′1 is either a direct bond or -Z-R wherein Z and R are as defined above, and
- X7 is —NH—NH2 in protected or unprotected form or —N3.
Dependencies are inferred from the claim text.