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Alpha helix cell-penetrating peptide multimer, preparation method therefor and use thereof

A technology of peptide multimer and multimer, which is applied in the field of α-helical cell penetrating peptide multimer, which can solve the problems of cytotoxicity and rupture

Inactive Publication Date: 2016-08-03
SEOUL NAT UNIV R&DB FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although cell penetrating peptides are peptides that have maximized ability to enter cells without damaging cells, cell membranes can be ruptured due to these cell penetrating peptides, and positively charged cell penetrating peptides can interact with negatively charged intracellular substances such as DNA or RNA meet, resulting in cytotoxicity

Method used

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  • Alpha helix cell-penetrating peptide multimer, preparation method therefor and use thereof
  • Alpha helix cell-penetrating peptide multimer, preparation method therefor and use thereof
  • Alpha helix cell-penetrating peptide multimer, preparation method therefor and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0130] Example 1: Synthesis of peptide monomers and dimers

[0131] Monomers LK (LKKLLKLLKKLLKLAG), monomers A (CKKLLKLCKKLLKLAG), B (LKKCLKLLKKCLKLAG), C (LKKLCKLLKKLCKLAG), D (LKKLLKCLKKLLKCAG) and E (LKKLLKLCKKLLKLCG), each with two half-cysteines, were synthesized using solid-phase synthesis method and Fmoc chemistry Amino acid residues, monomer AR (LRRLRLLLRRLLRLAG), wherein all K residues in the amino acid sequence of LK are substituted with R, monomers RA (CRRLLRLCRRRLLRLAG), RB (LRRCLRLLRRRCLRLAG), RC (LRRLCRLLRRLCRLAG), RD (LRRLLRCLRRRLRCAG) and RE(LRRLRLLCRRRLLRLCG), each having two cysteine ​​residues, and the like. Dimeric peptides with disulfides attached to them were obtained by oxidation of purified monomeric peptides under air oxidation conditions (dimers A, B, C, D, E, RA, RB, RC, RD and RE ). Such as image 3 As shown, the Dimal peptide was synthesized using a spacer according to the Michael reaction.

[0132] To observe the characteristics of cell pene...

Embodiment 2

[0134] Example 2: CD (Circular Dichroism) Analysis of Synthesized Peptides

[0135] CD (Circular Dichroism) was used to visualize the secondary structure of the synthesized monomeric, dimer and Dimal peptides. In particular, the dimers show close to 100% α-helical content even in aqueous environments. This α-helical content is very different from the monomer (30% in aqueous solution).

[0136] It is believed that when disulfide bonds exist at positions i and i+7 in one direction of the α-helix, two covalent bonds can maintain high α-helical content by combining the α-helical shape. Like dimeric peptides, Dimal peptides also have a high α-content because they are synthesized using two covalent bonds. However, Dimal peptides have a lower α-helical content than dimeric peptides due to the softness of the molecule.

[0137] Dimeric / Dimal peptides are treated with DTT which is a reducing environment (similar to the cytoplasmic environment). With this treatment it was possible...

Embodiment 3

[0138] Example 3: Cell Penetration Test of Peptides

[0139] The intracellular uptake of three different peptides was compared with each other by FACS experiments at different concentrations of FITC-labeled peptides ( Figure 4 ). At high peptide concentrations (500 nM), dimers (LK-3) and monomers (LK-1 or LK-2) showed high uptake efficiencies (90% or more) with little or no difference. However, at low concentration (10 nM), it was observed that the dimer (LK-3) showed a high uptake efficiency, while the uptake efficiency of the monomer was greatly reduced to less than 10%.

[0140] Specifically, it was observed that the Dimal peptide (LK-4) was taken up even at low concentrations, but its uptake efficiency was about 10-15% lower than that of the dimer (90% or more). The order of cell penetration ability at low concentration and high concentration is: dimer>Dimal>monomer.

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Abstract

The present invention relates to an alpha helix cell-penetrating peptide multimer, a preparation method therefor and a use thereof and, particularly, to a peptide multimer comprising a plurality of double-sided peptides, a preparation method of the peptide multimer, and a composition comprising the peptide multimer as an effective ingredient for preventing or treating HIV or a composition comprising the peptide multimer and a biological active substance for delivering an active substance into a cell.

Description

technical field [0001] The present invention relates to α-helical cell penetrating peptide multimers, methods for their preparation and uses thereof, and more particularly, to peptide multimers comprising a plurality of amphipathic peptides, methods for preparing said peptide multimers, A composition comprising the peptide multimer as an active ingredient for preventing or treating HIV and a composition comprising the peptide multimer and a bioactive substance for intracellular delivery of the bioactive substance. Background technique [0002] Antimicrobial peptides (AMPs) are natural peptides produced from the host's primary immune response to protect the host from externally invading pathogens. It primarily damages the cell membrane of invading pathogens thereby controlling the invading pathogens. However, some evidence has recently suggested that such antimicrobial peptides may control invading pathogens through mechanisms other than those by which antimicrobial peptides...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K7/02A61K47/42
CPCA61P31/18C07K7/08A61K38/10A61K47/64C07K2319/00A61K31/713A61K38/00A61K47/42C12N15/113C12N2310/14C12N2320/32
Inventor 俞载勋李衍玄纯实蒋尚穆
Owner SEOUL NAT UNIV R&DB FOUND
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