WO2022263695A1 - Peptides ayant une activité antimicrobienne et leurs utilisations - Google Patents
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the present invention refers to antimicrobial peptides (PAMs), both isolated and forming part of other polypeptide sequences and supramoecular structures, and their uses for the treatment and/or prevention of infections caused by bacteria, viruses, yeasts or fungi in living beings. , as well as for ex vivo disinfection of any type of surface. Therefore, the invention falls within the field of medicine and microbiology.
- PAMs antimicrobial peptides
- Non-traditional antimicrobial therapies currently under investigation include antimicrobial peptides (PAMs) (Datta, S.; Roy, 2021, int. J. Pept. Res. Tber., 27, 555-577). These are peptides of natural origin, present in practically all forms of life, and which are part of the host's defenses since they have antimicrobial properties and participate in the innate immune defense. PAMs represent a large and diverse group and are capable of killing or reducing the growth of invasive microorganisms, as well as enhancing innate and acquired immunity mechanisms.
- PAMs can cause cell death by modulating the immune system or directly, through disruptive or non-disruptive mechanisms of the plasma membrane (Raheem, N.; Straus, SK, 2019, Front. Microbiol., 10, 2886).
- the antimicrobial activity of these peptides may therefore be due to two different mechanisms of action: a) membrane disruptive mechanism, by which the peptide interacts and inserts itself into said membrane, forming pores, according to the "barrel-stick” models, "carpet”,”toroidalpores”,”molecularelectroporation” or “sinking raft”, and b) non-disruptive membrane mechanism, for e! which the peptide interacts with intracellular targets such as DNA, RNA and proteins.
- PAMs have been presented as promising candidates to combat microorganisms resistant to multiple drugs, due to their rapid action and broad spectrum of activity (Di Somma, A.; et a/,, 2020, Biomolecuies, 10, 652 ). PAMs can occur in a wide range of molecular weights, structural conformation, site of action, and biological mechanism. However, despite being good therapeutic candidates, to date only a few PAMs are approved for clinical use, with poümixins being the best characterized (Zavascki, A., Goldani, L., Li, J. and National, R., 2007, Journal o ⁇ Antimicrobia I Chemotherapy, 60(6), pp.1206-1215).
- Peptide therapy compared to small drugs, presents advantages from the perspective of safety, since its degradation products are natural amino acids and, furthermore, due to their short half-life, they do not tend to accumulate in tissues.
- therapeutic peptides even synthetic ones, are generally less immunogenic than recombinant proteins and antibodies.
- a good number of PAMs are in the last phases of clinical development (Nuti, R.; et al, 2017, Curr. Med. Chem., 24, 4303-4314).
- PAMs are those peptides formed by a chain of amino acids in an antipathic ⁇ -helix structure, such as cecropin and magaine. This type of structure generally has an affinity for biological membranes (Gagnon, MC; e ⁇ ai, 2017, Biochemistry, 56, 1680-1695).
- Patent US5847G47 describes the design of synthetic peptides consisting of a heptad repeat of leucines and lysines designed to adopt a structure of this type, and have antimicrobial activity against Escherichia cali and Staphylococcus aureus in concentrations of the order of 8- 63 pg/mL.
- the inventors have designed two antimicrobial peptides (PAMs) that, in the presence of biological membranes, are structured in antipathic ⁇ -helix conformation, and exhibit antimicrobial activity.
- PAMs antimicrobial peptides
- the present invention refers to the peptides as described in the claims and their uses as antimicrobial agents, in general, that is, both as a medicine for the treatment and/or prevention of diseases and infections caused by bacteria, both gram-positive and gram-negative, viruses, yeasts or fungi in a subject, as well as for the ex vivo disinfection of any type of surface, material, etc.
- the amino acid sequence of two peptides is described, the first called Bio2-3A of SEQ ID NO: 1 (YSKIAQDAAKLFDSLVK) and the second called 2X ⁇ B ⁇ o2 ⁇ 3A of SEQ ID NO: 2
- the mechanism of action of these peptides is the permeabilization of the membrane of microorganisms, thus reducing their viability.
- the peptides of the invention have antibacterial activity, more preferably against gram-positive bacteria, even more preferably belonging to the genus Streptococcus, and even more preferably belonging to the species Streptococcus pneumoniae (pneumococcus).
- the peptides of the invention have been shown to have an important antimicrobial effect, which makes them good candidates for PAMs, preferably against bacteria and more particularly against pneumococcus.
- a first aspect of the invention refers to an isolated peptide comprising SEQ ID NQ: 1 (Bio2-3A), from now on "the peptide of the invention".
- the peptide of the invention may comprise one or more repetitions of SEQ ID NO: 1 in its sequence, where said repetitions are separated or not by additional amino acids.
- the peptide of the invention comprises SEQ ID NO: 2 (2X-BI02-3A).
- the peptide of the invention may be fused to other proteins or peptides with an antimicrobial effect, either at its N- or C-terminus, or within the sequence of the peptide of the invention.
- the peptide of the invention consists of SEQ ID NO: 1 or SEQ ID NQ: 2, preferably SEQ ID NO: 2.
- the peptide of the present invention can be synthesized, for example, but not limited to, in viiro. For example, by solid phase peptide synthesis or by recombinant DNA approaches.
- the peptide of the invention can be produced recombinantly, not only directly but also as a fusion polypeptide together with a heterologous peptide, which can contain, for example, but not limited to, a signal sequence or other peptide having a cleavage site.
- a protease for example, but not limited to, at the N-terminus of the mature protein or peptide.
- polynucleotide of the invention refers to a polynucleotide encoding the peptide of the invention, hereinafter "polynucleotide of the invention”.
- nucleotide sequence refers to a polymeric form of nucleotides of any length that may or may not be chemically or biochemically modified. They refer, therefore, to any polyribonucleotide or polydeoxyribonucleotide, both single-stranded and double-stranded.
- the polynucleotide of the invention can be obtained artificially by conventional cloning and selection methods, or by sequencing.
- polynucleotide in addition to the coding sequence, can carry other elements, such as, but not limited to, introns, non-coding sequences in ios 5' or 3' ends, ribosome binding sites, or stabilizer sequences.
- These polynucleotides may additionally also include coding sequences for additional amino acids that may be useful, for example, but not limited to, to increase the stability of the peptide generated therefrom or to allow better purification thereof.
- Another aspect of the invention refers to a genetic construction comprising the polynucleotide of the invention, hereinafter "genetic construction of the invention".
- Said construction can also comprise all the necessary elements for the expression of the polynucleotide of the invention in a eukaryotic or prokaryotic host cell, such as promoters, "enhancers", terminators, etc.
- Another aspect of the invention refers to a cell comprising the genetic construction of the invention, from now on "cell of the invention”.
- This cell expresses, preferably recombinantly, the peptide of the invention. More preferably, this cell of the invention is used in a bioreactor for the production, in the laboratory or on a large scale, of the peptide of the invention.
- composition of the invention refers to a composition comprising the peptide of the invention, preferably the peptide consisting of SEQ ID NO: 2, hereinafter "composition of the invention”.
- composition of the invention is a pharmaceutical or veterinary composition.
- composition of the invention also comprises another active principle.
- the term "active principle”, “active substance”, “pharmaceutically active substance”, “active ingredient” or “pharmaceutically active ingredient” means any component that potentially provides a pharmacological activity in the cure, mitigation, treatment, or prevention of a disease or infection, preferably bacterial, or that affects the structure or function of the body of man or other animals.
- the other active ingredient to which the invention relates is an antimicrobial, preferably antibacterial agent, including, but without limiting our, antibiotics or antifungals.
- antimicrobial agent is understood to mean any chemical compound (synthetic or natural), peptide, polypeptide or nucleic acid (natural, recombinant or synthetic), which exhibits and exerts antibacterial, antifungal, antiviral and/or anti-yeast activity.
- the antimicrobial agent as an additional active ingredient present in the composition of the invention is one that does not exert a negative effect on the peptide of the invention and on its activity, that is, said antimicrobial agent is compatible with the activity of the peptide of the invention.
- the peptide of the invention could enhance the antimicrobial effect of the additional active principle present in the composition of the invention, for example by increasing the accessibility of the latter thanks to the power cell membrane permeabilizer exerted by the peptide of the invention.
- composition of the invention may also comprise, and as previously indicated, the peptide of the invention where it is fused to another protein/s or peptide/s with antimicrobial effect, either at its N- or C-terminal -terminai, or inside the sequence, so that the peptide of the invention favors the access of the other antimicrobial protein to its bacterial target through permeation of the cell membrane.
- the antimicrobial agent is an antimicrobial protein that is fused to the peptide of the invention, forming a single polypeptide chain.
- composition of the invention may also comprise other elements that help to preserve the structure and function of the peptide of the invention included in it, such as agents to protect it from degradation by proteases or excipients that improve its solubility.
- Another aspect of the invention refers to the non-therapeutic use of the peptide of the invention or the composition of the invention as a disinfectant agent, preferably for the disinfection of inert surfaces, that is, ex vivo.
- ex vivo surfaces any inert surface found outside the human or animal body.
- surfaces are, but are not limited to, any support, including industrial, household, clinical, or laboratory materials and surfaces, medical and veterinary devices, implants, catheters, and endotracheal tubes, tools, contact lenses, food, tubes, ventilation, fans, etc.
- Another aspect of the invention refers to the peptide of the invention or to the composition of the invention, for use as a medicine, preferably as a medicine for the treatment and/or prevention of infections caused by microorganisms selected from the list consisting of: bacteria , fungi, yeasts and/or viruses, more preferably bacteria.
- the bacteria are gram-positive, more preferably the gram-positive bacteria belong to the genus Sireptococcus, even more preferably the bacteria belong to the species S. pneumoniae (pneumococcus).
- the S. pneumoniae pathogen to which the present invention relates is resistant to conventional antibiotics.
- the medication to which the present invention refers is for the treatment and/or prevention of a disease selected from the list consisting of: meningitis, otitis media, sinusitis, septicemia or pneumonia. All of these diseases are caused by infection with the pathogen S. pneumoniae.
- the medicine of the invention is for the treatment and/or prevention of infections caused by bacteria belonging to the species S. pneumoniae and where said infections have caused a disease selected from the list consisting of: meningitis, otitis media , sinusitis, sepsis or pneumonia.
- drug refers to any substance used for the prevention, alleviation, treatment or cure of infections or diseases in humans and animals. In the context of the present invention it refers to a composition comprising the peptide or composition of the invention.
- the medicament of the invention comprises the peptide or composition of the invention in a therapeutically effective amount, which is capable of reducing the viability of infection-inducing microorganisms in the organism to which it is administered.
- therapeutically effective amount refers to the amount of peptide of the invention that produces the desired effect and the dosage to obtain a therapeutically effective amount will depend on a variety of factors, such as, for example, the age, weight, sex or tolerance of the individual to whom the medicament of the invention is going to be administered.
- the medicaments of the invention can be used either alone or in combination with other medicaments or compositions for the treatment or prevention of infections caused by bacteria, fungi, yeasts or viruses.
- the compositions of the present invention can be used together with other active principles or therapies as a combination therapy.
- the other active principles can be part of the same composition or they can be provided by means of a different composition, being administered at the same time or at different times.
- prevention consists of avoiding the appearance of damage caused by infections caused by bacteria, fungi, yeasts or viruses.
- treatment means combating the effects caused as a result of infections caused by bacteria, fungi, yeasts or viruses, to stabilize the condition of individuals or prevent further damage.
- the medicine to which the present invention refers can be for human or veterinary use.
- “Medicine for human use” is any substance or combination of substances that is presented as possessing properties for the treatment or prevention of disease in humans or that can be used in humans or administered to humans in order to restore, correct or modify physiological functions by exerting a pharmacological, immunological or metabolic action.
- the “medicine for veterinary use” is any substance or combination of substances that is presented as possessing curative or preventive properties with respect to animal diseases or that can be administered to the animal in order to restore, correct or modify its physiological functions by exercising a pharmacological, immunological or metabolic action.
- the medicament of the invention is intended for use in mammals, more preferably in humans.
- the medication of the invention may comprise other elements, such as pharmaceutically acceptable excipients, adjuvants or vehicles.
- excipient refers to a substance that helps the absorption of the elements of the composition of the invention, stabilizes and/or softens said elements, activates or helps the preparation of the composition in the sense of giving it consistency or providing flavors that make it more enjoyable.
- the excipients could have the function of keeping the ingredients together, such as is the case of starches, sugars or celluloses, the function of sweetening, the function of coloring, the function of protecting the composition, such as, for example, to isolate it from air and/or humidity, the filling function of a pill, capsule or any other form of presentation, such as, for example, is the case of dibasic calcium phosphate, the disintegrating function to facilitate the dissolution of the components and its absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph.
- the "vehicle”, like the excipient, is a substance that is used in the composition to dilute any of the components of the present invention included in it up to a determined volume or weight.
- the pharmacologically acceptable vehicle is an inert substance or one with a similar action to any of the elements of the present invention.
- the function of the vehicle is to facilitate the incorporation of other elements, to allow a better dosage and administration or to give consistency and shape to the composition.
- the presentation form is liquid
- the pharmacologically acceptable vehicle is the diluent.
- Pharmaceutical carriers can be liquid, such as water, solvents, oils, or surfactants, including those of petroleum, animal, vegetable, or synthetic origin, such as, for example, and not limited to, peanut oil, soybean oil, mineral oil, oil sesame, castor oils, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxygens, poloxamers, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, digltonin and the like.
- solvents, oils, or surfactants including those of petroleum, animal, vegetable, or synthetic origin, such as, for example, and not limited to, peanut oil, soybean oil, mineral oil, oil sesame, castor oils, polysorbates, sorbitan esters, ether sulfates, sulfates, betaines, glycosides, maltosides, fatty alcohols, nonoxygens, poloxamers, polyoxyethylenes
- compositions of the invention can be administered together with a sustained release vehicle.
- sustained release is used in the conventional sense to refer to a compound delivery system that provides gradual release of said compound over a period of time and preferably, though not necessarily, with relatively constant release levels of the compound over time. over a period of time.
- Illustrative examples of vehicles or Sustained release systems include, but are not limited to, liposomes, mixed liposomes, oleosomes, niosomes, ethosomes, miicapsules, microcapsules, nanocapsules, sponges, cyclodextrins, vesicles, micelles, mixed surfactant micelles, mixed phospholipid surfactant micelles, microspheres, microspheres, nanospheres, lipospheres, hydrogels, aerogels, microemulsions, nanoemulsions, miniparticles, microparticles, microparticles, nanoparticles, lipid solid nanoparticles, and nanostructured lipid supports.
- compositions of the invention can be presented in the form of a formulation selected from the group consisting of creams, multiple emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balms, foams, lotions, gels, cream gels, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, liniments, serums, soaps, shampoos, conditioners, serums, ointments, mousses, salves, powders, sticks, pencils, sprays, sprays, capsules, gelatin capsules, softgels, hard capsules, tablets, sugar-coated tablets, shapes granules, chewing gums, solutions, suspensions, emulsions, syrups, polysaccharide films, jellies and gelatin.
- compositions can be administered to an animal, including a mammal, and thus to man, in a variety of ways, including, but not limited to, parenteral, intraperitoneal, intravenous, intradermal, epidural, intraspinal, intrastromal, intraarticular, intrasynovial. !, intrathecal, intralesional, intraarterial!, intracardiac, intramuscular, intranasai, intracranial, subcutaneous, infraorbifai, infracapsuiar, topical, by transdermal patch or rectally, by administration of a suppository, percutaneous, nasal spray, surgical implant, internal surgical paint , infusion pump or via catheter.
- compositions of the present invention can be formulated for administration in a variety of ways known in the art.
- examples of pharmaceutical preparations include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions or emulsions) compositions for oral, topical, nasal, pulmonary, intravenous or parenteral administration, preferably oral, pulmonary administration. , intravenous, parenteral or combinations thereof.
- the pharmaceutical compositions containing the peptides of the present invention can also be formulated in the form of liposomes or nanospheres, sustained release formulations or any other system. conventional release.
- Another aspect of the invention refers to a method for the disinfection of inert surfaces (ex vivo) that comprises contacting the peptide of the invention or the composition of the invention with the surface to be disinfected.
- Another aspect of the invention refers to a method for the treatment and/or prevention of infections caused by microorganisms selected from the list consisting of: bacteria, fungi, yeasts and/or viruses, preferably bacteria, in the subject, which comprises administering the peptide of the invention or composition of the invention, in a therapeutically effective amount, to a subject in need thereof.
- bacteria are gram-positive, more preferably belonging to the genus Streptococcus, even more preferably belonging to the species S. pneumoniae.
- Fig. 1 Shows the result of the HeiiQuest program of the peptides Bio2-3A (A) and 2X-Bio2-3A (B). The tendency of the peptides to form an unfriendly helix is observed. The arrow indicates the estimated hydrophobic moment.
- Fig, 2 Shows the circular dichroism spectrum of the Bio2 ⁇ 3A and 2X-Bio2-3A peptides at 25 mM in 20 mM glycine buffer pH 3.0 in the absence or in the presence of 10 mM DPC. Residue molar ellipticity is plotted against wavelength. A conformational change from a random structure to an a-helix is observed, more pronounced in the case of the 2X-B ⁇ o2 ⁇ 3A peptide,
- Fig. 3 shows the CD spectrum of the peptides Bio2-3A (A) and 2X-BIO-3A (B) in the presence of increasing concentrations of DPC in 20 mM pH 3.0 glycine buffer.
- a change is observed from an unfolded conformation, with a peak centered at 200 nm, to an a-helical conformation in the presence of DPC, with characteristic peaks at 203 and 222 nm and an isodichroic point in each case, suggesting a transition between two States without intermediate species.
- Fig. 4 Shows the DC-followed titration of the Bio2-3A peptide and the 2X-Bio2 ⁇ 3A peptide in the presence of increasing concentrations of DPC in 20 mM pH glycine buffer 3.0.
- the conformation change is observed at concentrations above ia eme (1.25 mM) in the case of the Bio2-3A peptide while in the case of 2X-Bio2-3A it occurs at lower concentrations.
- Fig, 5. Shows the growth curves of a liquid culture of S. pneumoniae R8CIB17 in the presence and absence (same volume of 20 mM glycine buffer ph 3.0, but without peptide) of Bio2 ⁇ 3A peptide (A) and 2X peptide. -Bio2-3A (B). Each point represents the mean of the duplicates.
- Fig, 8. Shows ia cell viability of S. pneumonias in the presence and absence of the peptides Bio2 ⁇ 3A and 2X-Bio-3A at 210 min of the growth curve. As a control, cell viability is shown in the presence of the buffer containing the peptide (same volume of 20 mM glycine buffer pH 3.0, but without peptide). The mean of the triplicates of the logarithm of the number of colony-forming units per milliliter of culture is shown.
- Fig. 7 Shows the permeability of the membrane against the Sytox-Green probe of a culture of S. pneumoniae R6CIB17 after adding the 2X-Bio-3A peptide.
- the sample with Triton X-100 (a detergent) serves as a maximum permeability control.
- Example 1 Design and biophysical study of the peptides Bio2-3A and 2X-Bio2-3A.
- Peptide Bio2-3A (SEQ ID NO: 1) was theoretically designed in such a way that it exhibits a propensity to form an unfriendly a-helical structure, determined according to the HeliQuest program (Gautier, R.; et ai, 2008, Bioinformatics , 24, 2101-2102)
- B ⁇ 02-3A YSKIAQDAAKLFDSLVK (SEQ ID NO: 1)
- the 2X-Bio2-3A peptide is a duplication of Bio2-3A, with an intermediate serine and also presents a predisposition to form an amphipathic helical structure (Fig.1B): 2X-Bio2-3A: YSKIAQDAAKLFDSLVKSYSKIAQDAAKLFDSLVK (SEQ ID NO: 2)
- Equation 1 Q A represents the ellipticity at a given wavelength, [M] the molar concentration of protein or peptide, n the number of amino acids minus one, and d the path length in centimeters.
- the circular dichroism spectrum shows that both peptides (Fig. 2, solid lines) present a maximum peak around 200 nm in 20 mM glycine pH 3.0 buffer, indicating that they are mostly in a disordered conformation.
- DPC dodecylphosphocholine
- a titration was carried out at increasing concentrations of DPC (0-10 mM), as independent samples and at a fixed concentration of 25 mM peptide.
- Fig. 3 shows that the Bio2-3A peptide acquires the ⁇ -helix structure from 1.25 mM DPC (Fig. 4), a concentration that coincides with the CMC of the detergent, while the larger peptide ( 2X-Bio-3A) interacts even before micelles are formed, indicating that the peptide has a higher propensity to form a-helix and suggesting that it accumulates detergent half-micelles on its surface.
- a culture of Streptococcus pneumoniae of the strain R6CIB17a (non-flocculating strain derived from R8) was grown in liquid medium until an OD ssonm of 0.1, which corresponds to the beginning of the exponential phase. At that time, Bio2 ⁇ 3A peptide was added at a final concentration of 100 mM or 2X-Bio2 ⁇ 3A peptide at 10 and 50 mM concentrations.
- Fig. 5A shows that, in the case of the Bio2-3A peptide, once the stationary phase has been reached, at approximately 160 min, there is a marked decrease in OD ssonm to subsequently follow a pattern similar to that observed much later. in the control, result of the autolysis phase.
- the 2X-Bio2-3A peptide (Fig. 5B) at 10 mM only induces a retardation in the growth of the culture, but at a concentration of 50 mM it does not allow growth, and even induces lysis of the culture, since that D.O.ssonm data is obtained lower than the initial ones.
- Example 3 Effect of the 2X-Bio2-3A peptide on the permeability of the Streptococcus pneumoniae membrane.
- the experiment was carried out with a culture of cells grown to a OD,5s or nm of 0.6 in C+Y medium, at which time they were centrifuged and resuspended in a low ionic strength buffer (5 mM sodium phosphate, pH 7.0), to avoid problems of insolubility of the peptides and to which 280 mM of sorbitol was added to maintain the osmotic balance with the cells, together with Sytox Green at a concentration of 1 mM.
- a negative control was carried out, containing cells, Sytox and buffer, and a positive control.
- Fig. 7 shows the results, expressed as percent fluorescence relative to to the control of completely permeabilized cells, obtained by adding Triton X-100 to 1%.
- the minimum inhibitory concentration (MIC) of the 2X-Bio2-3A peptide was determined using Clinical and Laboratory Standards Institute (CLSI) criteria. (2009). Performance standards for antimicrobial susceptibility testing; 19th informationa! supplement.
- CLSI documents M1Q0-S19. CLSI, Wayne, PA .) by means of the microdiiuconstruucide system, following the indications described in the International Standard ISO 20776 and using the strains of pneumococcus R6 (non-capsulated) and D39 (capsulated strain, and therefore infective).
- the MIC was calculated as the lowest concentration of the agent at which growth is visibly inhibited.
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Abstract
La présente invention concerne des peptides, tant isolés que faisant partie d'autres séquences polypeptidiques et de structures supramoléculaires ; et des utilisations de ceux-ci comme agents antimicrobiens, tant comme médicament pour le traitement et/ou la prévention de maladies et d'infections provoquées par des bactéries, tant gram-positives que gram-négatives, des virus, des levures ou des champignons chez un sujet, notamment pour la désinfection ex vivo de n'importe quel type de surface inerte. L'invention concerne également des compositions et des médicaments comprenant lesdits peptides.
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017048092A1 (fr) * | 2015-09-17 | 2017-03-23 | 서울대학교산학협력단 | Peptide ou analogue de peptide hélicoïdal cassé ou plié présentant une activité antimicrobienne contre les bactéries gram-négatif, et utilisation de ce dernier |
WO2018094403A1 (fr) * | 2016-11-21 | 2018-05-24 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Nouvelle thérapie antimicrobienne et anticancéreuse |
EP3351553A1 (fr) * | 2015-09-17 | 2018-07-25 | Seoul National University R & DB Foundation | Peptide ou analogue de peptide hélicoïdal cassé ou plié présentant une activité antimicrobienne contre les bactéries gram-négatif, et utilisation de ce dernier |
WO2018195329A1 (fr) * | 2017-04-19 | 2018-10-25 | The Regents Of The University Of Colorado, A Body Corporate | Peptides antimicrobiens et méthodes de traitement d'agents pathogènes à gram négatif : analogues à face polaire et non polaire |
CN109553657A (zh) * | 2018-11-30 | 2019-04-02 | 东北农业大学 | 一种非完美两亲性肽w4及其制备方法和应用 |
WO2020150313A1 (fr) * | 2019-01-18 | 2020-07-23 | The Regents Of The University Of Colorado, A Body Corporate | Peptides antimicrobiens alpha-hélicoïdaux amphipathiques pour le traitement d'infections par des agents pathogènes à gram-négatif |
-
2021
- 2021-06-16 ES ES202130558A patent/ES2931001A1/es not_active Withdrawn
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Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2017048092A1 (fr) * | 2015-09-17 | 2017-03-23 | 서울대학교산학협력단 | Peptide ou analogue de peptide hélicoïdal cassé ou plié présentant une activité antimicrobienne contre les bactéries gram-négatif, et utilisation de ce dernier |
EP3351553A1 (fr) * | 2015-09-17 | 2018-07-25 | Seoul National University R & DB Foundation | Peptide ou analogue de peptide hélicoïdal cassé ou plié présentant une activité antimicrobienne contre les bactéries gram-négatif, et utilisation de ce dernier |
WO2018094403A1 (fr) * | 2016-11-21 | 2018-05-24 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Nouvelle thérapie antimicrobienne et anticancéreuse |
WO2018195329A1 (fr) * | 2017-04-19 | 2018-10-25 | The Regents Of The University Of Colorado, A Body Corporate | Peptides antimicrobiens et méthodes de traitement d'agents pathogènes à gram négatif : analogues à face polaire et non polaire |
CN109553657A (zh) * | 2018-11-30 | 2019-04-02 | 东北农业大学 | 一种非完美两亲性肽w4及其制备方法和应用 |
WO2020150313A1 (fr) * | 2019-01-18 | 2020-07-23 | The Regents Of The University Of Colorado, A Body Corporate | Peptides antimicrobiens alpha-hélicoïdaux amphipathiques pour le traitement d'infections par des agents pathogènes à gram-négatif |
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