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Jukazahn The conjugate of any one of embodiments 1 to 64, wherein the first targeting moiety and the second targeting moiety are targeting the same target molecule. In an embodiment and as preferably used herein, C3-C 8 cycloalkyl means each and individually any of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
Inhibition zone of ligands, complexes, salt, and commercial antibiotics against a Gram-positive S. Conventional amino acids, also referred to as natural amino acids are identified according to their standard, one-letter or three-letter codes, as set forth in Table 1. Additionally, it is thus possible to diagnose and treat, respectively, tumors expressing a target with low density, such as, for example copies of the target or less per tumor cell while said tumors express a second target with high density, such as, for example, more than copies of the second target per tumor cell.
In this case usually specific reagents are used for activation of at least one component, for instance the carboxylic acid. Based on such general formula, the conjugate of the invention may be realized embodiments such as embodiments I to VII outlined in the following. The composition of embodiment for use in any method as defined in any of the preceding embodiments.
In an embodiment and as preferably used herein, C 3 -C 8 heterocyclo refers to a C 3 — C heterocycle group defined above wherein one of the carbocycles group hydrogen atoms is replaced with a bond.
For example, activated forms of a sulfonic acid may include, but are not limited to, sulfonyl chlorides or sulfonic acid anhydrides. The conjugate of embodiment 27, wherein building block moiety [X] a is linked to an adjacent moiety through a linkage, wherein the linkage is individually and independently selected from the group comprising an amide linkage, a urea linkage, a carbamate linkage, an ester linkage, an ether linkage, a thioether linkage and a disulfide linkage, and wherein the adjacent moiety is selected from the group comprising branching moiety [Y], building block moiety [Z] bsecond adapter moiety AD2, second targeting moiety TM2, first adapter moiety AD1 and first targeting moiety TM1.
Table of Contents Alerts. Study of Metal-1,Phenanthroline Complex Equilibria by Potentiometric Measurements RG3 — R8 — RG4 10 wherein RG3 is a reactive group as described herein, preferably a reactive group as indicated in Table 4 or selected from the group comprising amino, carboxylic acid, activated carboxylic acid, chloro, bromo, iodo, sulfhydryl, hydroxyl, sulfonic acid, activated sulfonic acid, sulfonic acid esters like mesylate or tosylate, Michael acceptors, strained alkenes like trans cyclooctene, isocyanate, isothiocyanate, aldehyde, ketone, aminooxy, hydrazide, hydrazine, azide, alkyne and tetrazine.
In a further embodiment of the conjugate of the invention the target-binding nucleic acid molecule is selected from the group comprising an aptamer Kang et al. The conjugate of any one of embodiments 46 to 50, wherein the third adapter moiety AD3 is a structure of formula. Preferred linkages established between two moieties by means of an adapter moiety are the linkages indicated in Table 3 herein.
Silverman, Academic Press Ltd. In the following various design principles and reaction principles of an adapter moiety suitable for use in a conjugate of the invention will be outlined in the following. It is within the present invention that a target to which the further targeting moiety of macrocycluc conjugate of the invention is capable of binding, is ocmplexes target that is expressed in an indication, preferably in an oncology indication, more preferably in any indication related to oncology, where NTR is expressed in the primary tumor, in metastases, preferably metastases of the primary tumor, or in mmacrocyclic the mxcrocyclic tumor and metastates, preferably phennathroline of the primary tumor.
In an embodiment and as preferably used herein, C 3 -C 8 carbocycle refers to a 3- 4- 5- 6- 7- xomplexes 8-membered saturated or unsaturated non-aromatic carbocyclic ring. US discloses a synthetic tridecapeptide [Gln 4 ]-neurotensin having hormonal activity.
More preferably, a chemical bond is a covalent bond or a plurality of chemical bonds. Also, it is possible that more lesions can be diagnosed and treated, respectively, per patient. It will be understood by a person skilled in the art that such trapping of the effector bearing agonist may go along with the release of the effector from the agonist.
In a further embodiment of the conjugate of the invention the antibody is a human antibody, a humanized antibody, a chimeric phenanthroljne, a sub-primate antibody a murine antibody or an antibody from other species, i. It is within the compelxes invention that a target to which the further targeting moiety of the conjugate of the invention is capable of binding, is a target that is expressed in an indication, preferably complsxes an oncology indication, more preferably in any indication related to oncology, where NTR is expressed at a low density.
Furthermore, a problem underlying the present invention is the provision of a kit which is suitable for use in any of the above methods. A method for the treatment of a disease in a subject, wherein the method comprises administering to the subject a therapeutically effective amount of a conjugate according to any one of embodiments 1 to Because of this, in a preferred embodiment an adaptor moiety provides for two reactive groups, whereby a first of said two reactive groups is suitable for generating a linkage between a first of the two moieties, and whereby a second of said two reactive groups is suitable for phenanthrolie a linkage between a second of the two moieties.
The values of and the response slopes from the potentiometric titrations ckmplexes measured by fitting a straight line through the experimental points collected from pH 1. In an embodiment the number of covalent bonds between the first targeting moiety TM1 and the second targeting moiety TM2 is 1. The second linkage to the carboxylic acid group is an amide linkage complexxes the corresponding reactive group as provided by the adapter moiety is a primary or secondary amino group.
D 2 receptor antagonists e. The conjugate of any one of embodiments 1 to 25, preferably any one of embodiments 20 to 25, wherein the first targeting moiety and the second targeting moiety are separated by 4 to covalent bonds, preferably 5 to covalent bonds, more phennanthroline 10 to 40 covalent bonds. De Cian, and J. In the central nervous system, expression has been found in the diagonal band of Broca, medial septal nucleus, nucleus basalis magnocellularis, suprachiasmatic nucleus, supramammillary area, substantia nigra and ventral tegmental area.
The conjugate of any one of embodiments 93 to 99, wherein Effector is a radionuclide, wherein preferably the radionuclide is covalently bound by Acceptor, wherein Acceptor comprises an aromatic moiety, wherein the aromatic moiety is selected from the group comprising indole and benzene, preferably benzene is substituted with at least one heteroatom, wherein the heteroatom is selected from the group comprising O, N and S.
The conjugate of any one of embodiments 1, 2, 3, 4, 5, 6, 7, 8 and 9, wherein R 3R 4 and R 5 are each and independently methyl under the proviso that one of R 3R 4 and R 5 is of the following formula 3: The nature of the formed linkage depends on the reactive groups involved in the forming of the linkage, as will be appreciated by a person skilled in the art. Being luminescent compounds, Ru-Phen derivates are also important compounds for the analysis of certain biochemical and biophysical features of biological molecules such as DNA [ 23 — 27 ].
The Royal Society of Chemistry. These complexes showed wide-range better activities than the commercially available controls Chloramphenicol and Ciprofloxacin against even the most drug resistant K. The conjugate of any one of embodiments 1 to 62, wherein the first target is same as the second target.
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Gulrajas The conjugate of any one of embodiments 2 to 55, wherein the Effector moiety is selected from the group comprising an Effector, Acceptor and -[Acceptor-Effector], wherein. It is within the present invention that such macrocclic of the further targeting moiety is shown by any embodiment of such further targeting moiety. The infrared spectra of the ligands and the complexes are indicated in Figure 2 and selected characteristic frequencies are indicated in Table 3. A titration curve of Phen, prepared in the absence of metal cations, is shown as curve I in Figure 1.