摘要:
The present application relates to a compound having a formula 1: B—R1-R2-M wherein B is a binding element for recognizing and binding a target; R1 is a first group of atoms for reacting with a functionality of the target so as to form a covalent bond with the target; R2 is a second group of atoms; R1 and R2 being such that the formation of the covalent bond between R1 and the target generates cleavage of the bond between R1 and R2 so as to free R2-M; and M is selected from the group consisting of a hydrogen atom and a pharmaceutically acceptable moiety. Alternatively, R1 and R2 can be inverted to form the formula II: B—R2-R1-M and being such that the formation of the covalent bond between R1 and the target generates cleavage of the bond between R1 and R2 so as to free R2-B.
摘要:
The present invention provides processes for the production of preformed albumin conjugates. In particular, the invention provides processes for the in-vitro conjugation of a therapeutic compound to recombinant albumin, wherein a therapeutic compound comprising a reactive group is contacted to recombinant albumin in solution to form a conjugate. The processes provide for conjugation to albumin species of increasing homogeneity. The resulting conjugate is purified by chromatography, in particular hydrophobic interaction chromatography comprising phenyl sepharose and butyl sepharose chromatography.
摘要:
The present invention relates to a method for separating albumin conjugate from unconjugated albumin in a solution comprising albumin conjugate and unconjugated albumin by loading the solution onto a hydrophobic support equilibrated in aqueous buffer having a high salt content; applying to the support a gradient of decreasing salt concentration; and collecting the eluted albumin conjugate.
摘要:
Modified anti-angiogenic peptides are disclosed. The modified peptides are capable of forming a peptidase stabilized anti-angiogenic peptide. The modified anti-angiogenic peptides, particularly modified kringle 5 peptides are capable of forming a conjugate with a blood protein. Conjugates are prepared from anti-angiogenic peptides, particularly kringle 5 peptides, by combining the peptide with a reactive functional group with a blood protein. The conjugates may be formed in vivo or ex vivo. The conjugates are administered to patients to provide an anti-angiogenic effect.
摘要:
The present invention relates to an insulin derivative comprising an insulin molecule and a reactive group for covalently bonding a blood component, wherein preferably the insulin molecule is human natural insulin molecule and the reactive group is coupled to an amino acid of the insulin molecule at a position selected from the positions Gly A1, Phe B1 and Lys B29.
摘要:
The present invention relates to a compound comprising a PYY peptide or a functional derivative thereof, which is coupled to a reactive group. Such a reactive group is capable of reacting on a blood component so as to form a stable covalent bond therewith. The present invention also relates to a conjugate comprising such a compound which is covalently bonded to a blood component. Moreover, the invention also relates to a method of enhancing, in a patient, the anti-obesity activity of a PYY peptide or functional derivative thereof.
摘要:
A method for protecting a peptide from peptidase activity in vivo, the peptide being composed of between 2 and 50 amino acids and having a C-terminus and an N-terminus and a C-terminus amino acid and an N-terminus amino acid is described. In the first step of the method, the peptide is modified by attaching a reactive group to the C-terminus amino acid, to the N-terminus amino acid, or to an amino acid located between the N-terminus and the C-terminus, such that the modified peptide is capable of forming a covalent bond in vivo with a reactive functionality on a blood component. In the next step, a covalent bond is formed between the reactive group and a reactive functionality on a blood component to form a peptide-blood component conjugate, thereby protecting said peptide from peptidase activity. The final step of the method involves the analyzing of the stability of the peptide-blood component conjugate to assess the protection of the peptide from peptidase activity.
摘要:
The present invention discloses novel compounds useful as alkaline phosphatase inhibitors and therapeutic agents. Preferably, the novel compounds are useful as selective inhibitors of human alkaline phosphatases as opposed to Escherichia coli alkaline phosphatases. The novel compounds can also be used as cancer therapeutic agents, anti-depressive agents, anti-anergic agents, and antihelminthic agents. The novel compounds have the following general formula: ##STR1## wherein R' is an aryl, aryl ether, aryl thioether, aromatic heterocyclic, aromatic heterocyclic thioether, or aromatic heterocyclic ether group. More preferably, R' is a phenyl or a pyridine. Most preferably, R' is of the following formula: ##STR2## 2-thiopyridine, or ##STR3## 2-oxypyridine. R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.1 ', R.sub.2 ', R.sub.3 ', R.sub.4 ', and R.sub.5 ' can be the same or different, and at least one of which is selected from the group consisting of: H, C.sub.1 -C.sub.6 alkyl, halo C.sub.1 -C.sub.6 alkyl, phenyl, C.sub.1 -C.sub.6 alkoxy, phenoxy, trifluoromethyl, nitro, amino, carboxy, and halo groups with the proviso that each novel compound has no more than three substituents. Hydrogen is not considered a substituent.
摘要:
The present invention provides methods of administering an insulinotropic peptide in an amount effective to treat a disorder or condition while reducing nausea side effect by administering to a subject in need thereof an insulinotropic peptide conjugated to albumin. The present invention also provides methods of selecting a subject for administration of a conjugated insulinotropic peptide. Exemplary disorders or conditions treatable with an insulinotropic peptide include obesity and type II diabetes.
摘要:
Modified insulinotropic peptides are disclosed. The modified insulinotropic peptides are capable of forming a peptidase stabilized insulinotropic peptide. The modified insulinotropic peptides are capable of forming covalent bonds with one or more blood components to form a conjugate. The conjugates may be formed in vivo or ex vivo. The modified peptides are administered to treat humans with diabetes and other related diseases.