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Lipidated cationic peptide-PEG compositions for nucleic acid delivery

A technology for cationic compounds and cationic peptides, which can be applied in the directions of non-active components of polymer compounds, peptides, and the use of microcapsules, which can solve problems such as difficulty in optimizing lipid formulations

Pending Publication Date: 2022-05-27
胡桃钳医疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] However, despite the promise of lipid nanoparticle formulations to achieve the desired properties for nucleic acid transfer in vivo, the optimization of lipid formulations is often difficult due to the interplay of many variables, including identifying compatible co-components for the nucleic acids to be delivered. and carefully adjust the relative amounts of each component to achieve the desired pharmacokinetic properties

Method used

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  • Lipidated cationic peptide-PEG compositions for nucleic acid delivery
  • Lipidated cationic peptide-PEG compositions for nucleic acid delivery
  • Lipidated cationic peptide-PEG compositions for nucleic acid delivery

Examples

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example

[0442] The present disclosure is described in further detail in the following examples, which are not intended to limit the scope of the claimed disclosure in any way. The accompanying drawings are intended to be considered an integral part of the specification and description of the present disclosure. The following examples are offered to illustrate, but not limit, the claimed disclosure.

example 1

[0443] Example 1 - Synthesis of Exemplary Tertiary Aminolipidated Cationic Peptides for Nucleic Acid Delivery

[0444] The following examples describe general protocols for the synthesis of tertiary aminoesterified and / or PEGylated cationic peptide compounds of formula (I) as described herein.

[0445]

[0446] In the description provided below, all R a and R b Both are –H. All polymers were synthesized using bromoacetic acid and primary amines. Figures 2B-2E provided in R 2 , R 3 , R 4 , R 5 and R 6 Some exemplary substituents for primary amines at to prepare the tertiary aminoesterified and / or PEGylated cationic peptide compounds of the present disclosure.

[0447] Fmoc-Rink amide resin was used as a solid support. The Fmoc group on the resin was deprotected with 20% (v / v) piperidine-dimethylformamide (DMF). The amino resin is then amidated with bromoacetic acid. The a-carbon is subsequently aminated by nucleophilic displacement of the bromide with a primary a...

example 2

[0455] Example 2 - Synthesis and Characterization of Representative Aminolipidated Peptoids

[0456] Aminolipidated peptoids were synthesized by the submonomer method described in Example 1 above using bromoacetic acid and N,N'-diisopropylcarbodiimide (DIC). Polystyrene supported MBHA Fmoc protected Rink amide (200 mg representative scale, 0.64 mmol / g loading, Protein Technologies) resin was used as the solid support. For bromoacetylation, the resin was mixed with a 1:1 mixture of 2M bromoacetic acid and 2M N,N'-diisopropylcarbodiimide (DIC) for 5 minutes. Amine displacement was performed using a 1M solution of the amine in DMF for 1 hour. After synthesis, the crude peptoid was cleaved from the resin using 5 mL of a 95:2.5:2.5 mixture of trifluoroacetic acid (TFA):water:triisopropylsilane for 40 minutes at room temperature. The resin was removed by filtration and the filtrate was concentrated using a Biotage V10 evaporator. The crude peptoid was further concentrated by lyop...

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Abstract

The present disclosure relates to complexes and compositions of cationic compounds in combination with low mass percent pegylated compounds, such as pegylated lipids, for delivering nucleic acids and other polyanionic cargo to cells, methods for preparing complexes and compositions comprising one or more cationic compounds and low mass percent pegylated compounds and polyanionic compounds and methods for delivering polyanionic compounds to cells.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims priority to and the benefit of US Provisional Application No. 62 / 885,022, filed August 9, 2019, and US Provisional Application No. 62 / 907,470, filed September 27, 2019, of which The disclosure is incorporated herein by reference in its entirety. technical field [0003] The present disclosure relates to complexes and combinations of cationic compounds for delivery of nucleic acids and other polyanionic cargoes in combination with low mass percentages of PEGylated compounds such as PEGylated lipids or PEGylated diacylglycerol derivatives thing. More specifically, the present disclosure relates to tertiary aminolipidated and / or pegylated peptoids, and complexes and compositions thereof for nucleic acid delivery in combination with small amounts of pegylated lipids. The present disclosure also provides methods for preparing complexes and compositions thereof comprising one or more cationic compound...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K47/54A61K47/62A61K47/60C07K7/06C07K7/08C12N15/88
CPCA61K48/0041A61K47/543A61K47/62A61K47/60C07K7/06C07K7/08C12N15/88A61K47/42A61K47/6455
Inventor C·J·麦金来
Owner 胡桃钳医疗公司