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Dimeric thrombopoietin peptide mimetics binding to MP1 receptor and having thrombopoietic activity

A technology of receptor binding and compounds, applied in the field of compounds, can solve problems such as lack of sequence homology

Inactive Publication Date: 2006-08-02
AMGEN K A INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The 14-group peptide, named TMP (TPO Mimetic Peptide), has no significant sequence homology to TPO or MGDF

Method used

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  • Dimeric thrombopoietin peptide mimetics binding to MP1 receptor and having thrombopoietic activity
  • Dimeric thrombopoietin peptide mimetics binding to MP1 receptor and having thrombopoietic activity
  • Dimeric thrombopoietin peptide mimetics binding to MP1 receptor and having thrombopoietic activity

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[0099] Lysine and amino terminal residues can react with succinic acid or other carboxylic anhydrides. The effect of derivatization with these reagents is that the charge of lysine residues can be reversed. Other suitable reagents that can derivatize residues containing α-amino groups include: imidates such as methyl picolinimidate; pyridoxal phosphate; pyridoxal; chloroborohydride (Chloroborohydride); trinitrobenzene sulfonic acid; O-methyl isourea; 2,4-pentanedione; and transaminase-catalyzed reaction with glyoxylic acid.

[0100]Arginine residues can be modified by reacting with one or several conventional reagents, including phenylacetaldehyde, 2,3-butanedione, 1,2-cyclohexanedione, and ninhydrin. The derivatization of arginine residues needs to be carried out under alkaline conditions because the pKa of the guanidine functional group is very high. Moreover, these reagents can react with both the guanidine groups of lysine and arginine.

[0101] The specific modification of ty...

Embodiment

[0263] I. The following will introduce some examples of preparation methods of the first group of compounds disclosed here.

[0264] A. Materials and methods

[0265] All amino acid derivatives (all in L configuration) and resins used in peptide synthesis were purchased from Novabiochem. Peptide synthesis reagents (DCC, HOBt, etc.) were purchased from Applied Biosystems Co., Ltd. in solution form. Two PEG derivatives were purchased from Shearwater Polymers Co., Ltd. All solvents (dichloromethane, N-methylpyrrolidone, methanol, acetonitrile) were purchased from EM Sciences. HPLC analysis was performed on a Vydac column (0.46cm×25cm, C18 reversed phase, 5mm) of the Beckman system, the elution flow rate was 1ml / min, and dual UV detection was performed at 220 and 280nm. Two mobile phases of linear gradients were applied in all HPLC operations, buffer A-water (0.1% TFA) and buffer B-acetonitrile (0.1% TFA). The numbered peptides cited here, such as 17b, 18, 19, and 20, can be named wit...

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Abstract

The invention relates to the field of compounds, especially peptides or polypeptides, that have thrombopoietic activity. The peptides and polypeptides of the invention may be used to increase platelets or platelet precursors (e.g., megakaryocytes) in a mammal.

Description

[0001] This application is a divisional application of Chinese patent application 99812517.2 "Mimetic dimer thrombopoietin peptide that binds to MP1 receptor and has platelet production activity" on October 22, 1999. [0002] This application claims priority from U.S. Provisional Application 06 / 105 348 filed on October 23, 1998. Technical field [0003] Basically, the present invention relates to the field of compounds, especially peptides or polypeptides with thrombopoietic activity. The peptide or polypeptide of the present invention can be used in mammals to increase the production of platelets or platelet precursors (such as megakaryocytes). Background technique [0004] The present invention relates to the field of compounds, especially peptides that have the ability to stimulate the production of platelets and their precursor cells such as megakaryocytes in vitro and in vivo. Before discussing the properties of the compounds of the present invention, two proteins with platel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/52C12N15/19C12N5/10C12N1/21A61K38/19A61P7/06C12N15/09A61K38/00A61P7/00C07K19/00C12N1/15C12N1/19C12P21/02
CPCC07K7/08C07K14/524C07K2319/00C07K7/06A61K38/00C07K2319/30A61P43/00A61P7/00A61P7/04A61P7/06C07K14/52C07K2319/75
Inventor C·-F·刘U·菲格J·奇塔姆
Owner AMGEN K A INC
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