New conjugated molecules comprising peptide derived from CD4 receptor coupled to polyanionic polypeptide for treatment of AIDS

A technology of anionic polypeptides and conjugated molecules, which can be used in medical preparations containing active ingredients, medical preparations without active ingredients, receptors/cell surface antigens/cell surface determinants, etc. question

Inactive Publication Date: 2013-12-04
INST PASTEUR +2
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Mutations in either of these two sites wil

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • New conjugated molecules comprising peptide derived from CD4 receptor coupled to polyanionic polypeptide for treatment of AIDS
  • New conjugated molecules comprising peptide derived from CD4 receptor coupled to polyanionic polypeptide for treatment of AIDS
  • New conjugated molecules comprising peptide derived from CD4 receptor coupled to polyanionic polypeptide for treatment of AIDS

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0165] Embodiment 1: Synthesis of conjugated molecules of the present invention

[0166] 1.1 Synthesis of peptides of formula H-γ-Abu-SXDXSXDXSXDXS-OH, wherein X=YSO3 (P3YSO3), Y(P3Y), Asu(P3Asu), or pF(P3pF); H-γ-Abu-SY SO3 Dy SO3 Sy SO3 DYSYDYS-OH (Nter3 Sulfate); H-γ-Abu-SYDYSYDY SO3 Sy SO3 Dy SO3 S-OH (Cter3 Sulfate); and H-γ-Abu-(Glu) 13 -OH(E13); where γ-Abu:NH 2 -(CH 2 ) 3 -CO.

[0167] The following examples describe the synthesis of modified peptides of formula H-γ-Abu-SXDXSXDXSXDXS-OH, wherein X=YSO3(P3YSO3), Y(P3Y), Asu(P3Asu) or pF(P3pF); H-γ-Abu-SY SO3 Dy SO3 Sy SO3 DYSYDYS-OH (Nter3 Sulfate); H-γ-Abu-SYDYSYDY SO3 Sy SO3 Dy SO3 S-OH (Cter3 Sulfate); H-γ-Abu-(Glu) 13 -OH(E13); where γ-Abu:NH 2 -(CH 2 ) 3 -CO. In this formula, the anionic peptides of the present invention (except peptide E13) correspond to SXDXSXDXSXDXS-OH (SEQ ID NO: 19), where X is as above (same or different).

[0168] The resulting modified peptide is:

[0169] P3YSO3 (SEQ I...

Embodiment 2

[0196] Embodiment 2: Biacore evaluation

[0197] 2.1. Operation

[0198] Two different gp120s were employed, derived from an X4-type isolate (gp120MN) and an R5-type isolate (gp120YU2). The ability of different molecules to inhibit the interaction of gp120 with various receptors or co-receptors was measured by surface plasmon resonance (Biacore).

[0199] To this end, proteins (in this case the gp120 envelope protein) can be immobilized on a biosensor (Sensorchip CM4Biacore) according to the procedure described (Vivès et al. J. Biol. Chem. 279, 54327-54333, 2005). surface. When injected onto surfaces coated with the MN(X4) or YU2(R5) gp120 envelope, mCD4 binds and exposes the CD4i epitope on gp120 responsible for the envelope binding of mAb17b ( Figure 5 A) (mAb17b antibody recognizes CD4-induced epitopes and mimics co-receptors CCR5 or CXCR4). The interaction signal between gp120 and mAb17b was measured as a function of time when mCD4 or the compound to be tested was inj...

Embodiment 3

[0211] Embodiment 3: the antiviral activity of peptide of the present invention to X4-tropism HIV-1-LAI and R5-tropism HIV-1 / Ba-L strain

[0212] 3.1. Operation

[0213] Antiviral activity was performed as described in WO / 2009 / 098147 and Nature Chemical Biology, 2009, 5(10), 743-748.

[0214] Briefly, X4-tropic HIV-1-LAI was expanded and titrated in vitro on phytohemagglutinin-P (PHA-P)-activated peripheral blood mononuclear cells (PBMC) (Barre-Sinoussi, Science 220, 868 -71, 1983) or R5-tropic HIV-1 / Ba-L (Gartner et al., Science 233, 215-9, 1986) strain. use The formula for calculating the tissue culture infection dose ( Arch. Exp. Path. Pharmak. 162, 480-483, 1931). For antiviral assays, PHA-P-activated PBMCs were pretreated for 30 min with six concentrations of each drug (diluted 1:5 between 0.5 μM and 160 pM) and treated with X4-tropic LAI or R5-tropic Ba - Infection with one hundred and 50% tissue culture infectious dose (TCID50) of the L strain. Drugs were maintai...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

This invention relates to a conjugated molecule comprising a peptide derived from the CD4 receptor coupled to an organic molecule by means of a linker as well as a process for its preparation. Said organic molecule comprises a 13 amino acid anionic polypeptide. Such a conjugated molecule can be used in antiviral treatment, namely in the treatment of AIDS.

Description

technical field [0001] The present invention relates to conjugated molecules comprising a peptide derived from the CD4 receptor and an organic molecule, such as a polyanionic polypeptide. The conjugated molecule can be used for antiviral therapy, that is, for the treatment of AIDS. The invention further relates to methods of preparing said conjugated molecules. Background technique [0002] Triple therapy combining nucleosides (NRTIs), non-nucleosides (NNRTIs), and / or protease inhibitors (PIs) resulted in reductions in viral charge to below detectable levels in a large number of seropositive HIV patients. These treatments target both reverse transcription and proteolysis. This efficacy has resulted in a substantial reduction in the number of deaths caused by HIV infection. But unfortunately, about 80% of the patients showed antiviral resistant genotypes, and more worryingly, 45.5% of the viral populations were resistant to NRTI / PI combination therapy, while 26% were resis...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): A61K47/48C07K14/705A61P31/18
CPCC07K2319/00C07K7/06C07K7/08C07K14/70514C07K14/70539A61K47/48276C07K14/00A61K47/6425A61K38/195A61K38/16A61K38/177A61P31/18C07K17/02
Inventor F·巴勒斯克H·洛尔塔雅各布D·博纳夫
Owner INST PASTEUR
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap