Peptides enhancing CEH activity or ACAT inhibitory activity, pharmaceutical compositions comrising these peptides and their use in the treatment of atherosclerosis

A peptide and active technology, applied in the field of activating cholesterol mobilization and promoting release, can solve problems such as accelerated arteriosclerosis

Inactive Publication Date: 2006-09-20
QUEENS UNIV OF KINGSTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Today, the question of whether the acceleration of SAA expression observed in tissue injury is b

Method used

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  • Peptides enhancing CEH activity or ACAT inhibitory activity, pharmaceutical compositions comrising these peptides and their use in the treatment of atherosclerosis
  • Peptides enhancing CEH activity or ACAT inhibitory activity, pharmaceutical compositions comrising these peptides and their use in the treatment of atherosclerosis
  • Peptides enhancing CEH activity or ACAT inhibitory activity, pharmaceutical compositions comrising these peptides and their use in the treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0198] Example 1: Animals

[0199] 6-8 week-old female SD rats were obtained from Charles River, Montreal, Quebec, and placed in a 12-hour light-12-hour light-dark environment at constant temperature. Feed Purina laboratory mouse food tablets and water containing chlordiazepoxide.

[0200] ApoE knockout rats were obtained from Jackson Laboratory, Maine, USA.

Embodiment 2

[0201] Embodiment 2: chemical reagent

[0202] All chemicals were of reagent grade and purchased from Fisher Scientific (Nepean, Ont.), Sigma (St. Louis, MO), ICN (Aurora, OH), or BioRad (Hercules, CA). DMEM and FBS were purchased from (Burlinton, Ont.) radiolabeled [1-14C]-oleic acid (52mCi / ml), [1,2,6,7-3H(N)]-cholesterol (82mCi / ml ) was obtained from DuPont NEN (Boston, MA).

Embodiment 3

[0203] Example 3: Peptides

[0204] The following peptides were synthesized by solid-phase peptide synthesis in PEApplied Biosystems 433A peptide synthesizer using FMOC as the protecting group of amino acids.

[0205] GFFSFVHEAFQGAGDMWRAY (SEQ ID NO: 1)

[0206] TDMKEANWKNSDKYFHARGNYDAAQRGPGG (SEQ ID NO: 2)

[0207] VWAAEKISDGREAFQEFFGRGHEDTIADQE (SEQ ID NO: 3)

[0208] DTIADQEANRHGRSGKDPNYYRPPGLPDKY (SEQ ID NO: 4)

[0209] GFFSFIGEAFQGAGDMWRAY (SEQ ID NO: 5)

[0210] RSFFSFLGEAFDGARDMWRAYSD (SEQ ID NO: 6)

[0211] RGFFSFIGEAFQGAGDMWRAY (SEQ ID NO: 7)

[0212] ADQEANRHGRSGKDPNYYRPPGLPDKY (SEQ ID NO: 8)

[0213] ADQEANRHGRSGKDPNYYRPPGLPAKY (SEQ ID NO: 9)

[0214] ADQAANKWGRSGRDPNHFR (SEQ ID NO: 11)

[0215] ADQAANEWGRSGKDPNHFR (SEQ ID NO: 12)

[0216] The separation and purification of the peptides was accomplished by analytical HPLC and ion spray mass spectrometry, and the peptides were dialyzed with distilled water and freeze-dehydrated before use. ...

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Abstract

The present invention provides peptides derived from mammalian serum amyloid A2.1 and their mimics and compounds that have been screened to enhance the activity of macrophage cholesterol esterase and/or inhibit the activity of acyl-CoA:cholesterol transferase or compositions, and methods of treating coronary heart disease, cardiovascular disease, and arteriosclerosis using these compositions are provided.

Description

field of invention [0001] The role of peptides in inhibiting the accumulation of cholesterol in patients with inflammation or arteriosclerosis, as well as in activating cholesterol mobilization and promoting release, has been confirmed. The present invention relates to the separation of peptides, especially artificial synthesis of peptides, including the use of chemical methods and recombinant methods Synthetic peptides, mimetics of the above-mentioned peptides and compounds, and pharmaceutical compositions containing one or more of the above-mentioned peptides or part of the peptides or compounds or mimetics. In addition, the present invention also provides the use of the above-mentioned ingredients to treat coronary Heart disease, cardiovascular disease and methods of use in the treatment and / or prevention of arteriosclerosis and inflammation. Background of the invention [0002] Cardiovascular disease, including coronary artery disease caused by atherosclerosis, is the la...

Claims

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Application Information

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IPC IPC(8): C07K14/47C07K7/08A61K38/10A61K38/17A61K47/48A61K47/64
Inventor 罗伯特·奇斯维斯奇谭遂鹏约翰·B·安西贾宗超
Owner QUEENS UNIV OF KINGSTON
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