Hormone-toxin conjugate compounds
AssigneeColorado State University Research Foundation
InventorsTorrance M. Nett, Leonard M. Glode
Life of this patent
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Abstract
Certain toxic compounds (T) such as, for example, compounds based upon diphtheria toxin, ricin toxin, pseudomonas exotoxin, .alpha.-amanitin, pokeweed antiviral protein (PAP), ribosome inhibiting proteins, especially the ribosome inhibiting proteins of barley, wheat, corn, rye, gelonin and abrin, as well as certain cytotoxic chemicals such as, for example, melphalan and daunomycin can be conjugated to certain analogs of gonadotropin-releasing hormone to form a class of compounds which, when injected into an animal, destroy the gonadotrophs of the animal's anterior pituitary gland. Hence such compounds may be used to sterilize such animals and/or to treat certain sex hormone related diseases.
Claims17
A compound used for rendering gonadotrophs incapable of secreting gonadotropins, said compound having the general formula ##STR3## wherein T is a toxin group capable of precluding secretion of gonadotropin by said gonadotrophs;
- X is an amino acid selected from the group consisting of lysine, D-lysine, ornithine, D-ornithine, glutamic acid, D-glutamic acid, aspartic acid, D-aspartic acid, cysteine, D-cysteine, tyrosine and D-tyrosine;
- Y is a linking agent;
- and Z is a substituent selected from the group consisting of Gly-NH.sub.2, ethylamide, and AzA-Gly-NH.sub.2, said compound capable of being conveyed across a cell membrane of said gonadotrophs.
A hormone/toxin conjugate comprising a peptide hormone capable of binding to a GnRH receptor, conjugated to a toxin group, by a linking agent, said conjugate being capable of selectively binding to a gonadotroph and of substantially precluding said gonadotroph from secreting gonadotropins, said conjugate capable of being conveyed across a cell membrane of said gonadotrophs and said conjugate being capable, when administered in an effective amount to an animal, of sterilizing said animal without killing said animal.
A conjugate of claim 11, wherein said toxin group is a modified toxin comprising a toxic domain and a translocation domain but lacking a functional toxin cell binding domain.
A hormone/toxin conjugate comprising:
- (a) a toxic domain of a toxin;
- (b) a modified B-chain of a toxin that is capable of promoting translocation of said toxic domain across a cell membrane but is modified so as to be devoid of intrinsic binding activity;
- (c) a hormone which is capable of selectively binding to a receptor on a gonadotroph;
- (d) a linking agent that conjugates said toxin to said hormone;
- and
- (e) whereby said conjugate, when administered to an animal in an effective amount, is capable of sterilizing said animal without killing said animal.
Dependencies are inferred from the claim text.