KR102166543B1 - Composition and Method for Inhibiting Keloid - Google Patents

Abstract

The present invention relates to a composition for inhibiting keloids. More specifically, it relates to a peptide derived from telomerase and a composition comprising the same, which is effective for inhibiting keloids. A composition comprising a peptide having a sequence of SEQ ID NO according to the present invention or a peptide or a fragment having a sequence having 80% homology with the sequence has an excellent effect on inhibiting keloids. Therefore, through the composition of the present invention, it is possible to inhibit the growth of keratinocytes and effectively inhibit the proliferation of keloids.

Description

Composition and Method for Inhibiting Keloid {Composition and Method for Inhibiting Keloid}

The present invention relates to a composition for inhibiting keloids. More specifically, it relates to a composition for inhibiting keloids comprising a peptide derived from telomerase.

A keloid is an abnormal proliferation of tissues that are caused by skin bonding and formed in wound tissue in the process of skin regeneration after skin damage. Keloids are biologically malignant and can continue to proliferate beyond the edges of the injury. When a keloid occurs, the lesion becomes hard, and the elasticity of the skin is significantly limited, resulting in pain in the affected area. In addition, when the keloid is applied to the joint, the range of motion of the joint can be significantly limited. When keloids occur in children, they may cause impaired growth in the lesion.

Currently, several methods are proposed for such keloids, but these conventional methods are known to have respective problems. Ⅰ) The surgical removal of keloids is highly likely to cause recurrence, and there is a risk of growing keloids larger than before removal. Ii) The keloid treatment method using a wet dressing made of silicone gel, which is known to cause a moisturizing effect, has an inconsistent effect, and when applied for a long time, there is a problem of severe itching.

Therefore, if a method having a keloid suppression effect without side effects is developed, it can be used to effectively perform keloid suppression.

EP 1 093 381 B1

Accordingly, the present inventors have made great efforts to develop a composition that has an excellent effect on suppressing keloids and does not have side effects, resulting in the completion of the present invention.

The present inventors discovered that a peptide derived from telomerase can have an excellent effect as a composition for inhibiting keloids, and thus completed the present invention.

An object of the present invention is to provide a composition for inhibiting keloids.

According to one aspect of the present invention, a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a peptide that is a fragment thereof, and the peptide in an amount effective to inhibit keloids Containing, a composition for inhibiting keloids is provided.

In the composition for inhibiting keloid according to another aspect of the present invention, the fragment may be a fragment consisting of three or more amino acids.

In the composition for inhibiting keloids according to another aspect of the present invention, the inhibition of keloids may be for administration to an individual in need of inhibiting the growth of keratinocytes.

In the composition for inhibiting keloids according to another aspect of the present invention, the peptide may be derived from human telomerase.

According to an aspect of the present invention, the composition for inhibiting keloids according to the present invention; And a kit for suppressing keloids including instructions is provided.

According to one aspect of the present invention, keloid inhibition comprising administering a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a peptide that is a fragment thereof to a subject in need of keloid inhibition A way is provided.

A composition comprising a peptide having a sequence of SEQ ID NOs according to the present invention, a peptide having a sequence having a sequence of 80% or more homology to the sequence, or a peptide, which is a fragment thereof, has an excellent effect on suppressing keloids. Therefore, the composition of the present invention can be effectively used for keloid inhibition.

1 is a relative change in cell proliferation in the PEP 1 40 μM treatment group when the growth of a group cultured in a medium (Control without PEP 1 treatment) is set to 1 in order to confirm the effect of PEP 1 on inhibiting the proliferation of HaCaT cells. It is a cell growth curve graph showing the ratio (ratio).
Figure 2 is a PEP 1 In order to measure the keloid inhibitory efficacy, this is a photograph of analyzing the results of performing a scratch assay. Specifically, inject 5x10 ⁵ HaCaT cells for each microparticle into 6 microcell culture plates, stabilize them overnight and incubate them with 90% or more confluence, and then use a sterilized 200 μl pipette tip to micronize them. I scratched the center part of the body once vertically to hurt it. Thereafter, the control medium and the PEP 1 40 μM treatment group were divided into two groups, followed immediately (after 0 hours), 12 hours, 36 hours, and 52 hours, and observed under a microscope.

Since the present invention can apply various transformations and have various embodiments, the present invention will be described in more detail below based on the embodiments. However, these examples are not intended to limit the present invention to a specific embodiment, and the present invention is capable of various examples and applications based on what is described in the claims, and all included in the spirit and scope of the present invention. It should be understood to include transformations, equivalents or substitutes. In describing the present invention, when it is determined that a detailed description of a related known technology may obscure the subject matter of the present invention, a detailed description thereof will be omitted.

Telomere is a genetic material that is repetitively present at the end of a chromosome, and is known to prevent damage to the chromosome or binding to other chromosomes. Each time a cell divides, the length of the telomeres decreases little by little. If there are more than a certain number of cell divisions, the telomeres become very short, and the cells stop dividing and die. On the other hand, it is known that lengthening telomeres extends the lifespan of cells. For example, cancer cells secrete an enzyme called telomerase to prevent shortening of telomeres, so it is known that cancer cells can continue to proliferate without dying. The present inventors have confirmed that a composition comprising a peptide derived from telomerase is effective in inhibiting keloids and completed the present invention.

In one aspect of the present invention, the peptide of SEQ ID NO: 1, a peptide that is a fragment of SEQ ID NO: 1, or a peptide having a sequence homology of 80% or more with the peptide sequence is a telomerase, specifically in human (Homo sapiens) telomerase. It includes derived peptides.

The peptides listed in SEQ ID NO: 1 are shown in Table 1 below. The "name" in Table 2 below is named to distinguish the peptide. In one aspect of the invention, the peptide set forth in SEQ ID NO: 1 represents the entire peptide of human telomerase. In another aspect of the present invention, a peptide having the sequence of SEQ ID NO: 1, a peptide that is a fragment of the sequence of SEQ ID NO: 1, or a peptide having a sequence homology of 80% or more with the peptide sequence is a corresponding among the peptides included in telomerase. It includes "synthetic peptides" obtained by selecting and synthesizing a peptide at a position. SEQ ID NO: 2 shows the amino acid sequence of all telomerase.

The peptides disclosed herein may include peptides having sequence homology of 80% or more, 85% or more, 90% or more, 95% or more, 96% or more, 97% or more, 98% or more, 99% or more. In addition, the peptide disclosed herein is a peptide comprising SEQ ID NO: 1 or fragments thereof and one or more amino acids, two or more amino acids, three or more amino acids, 4 or more amino acids, 5 or more amino acids, 6 or more amino acids. Alternatively, it may include a peptide in which 7 or more amino acids have been changed.

In one aspect of the present invention, amino acid changes belong to properties that cause the physicochemical properties of the peptide to be altered. For example, amino acid changes such as improving the thermal stability of the peptide, altering the substrate specificity, changing the optimum pH, and the like can be performed.

The term "amino acid" as used herein includes the 22 standard amino acids that are naturally incorporated into a peptide, as well as D-isomers and modified amino acids. Accordingly, in one aspect of the present invention, the peptide may be a peptide containing D-amino acid. Meanwhile, in another aspect of the present invention, the peptide may include a non-standard amino acid that has been modified after translation (post-translational modification). Examples of post-translational modifications include phosphorylation, glycosylation, acylation (e.g., acetylation, myristoylation and palmitoylation, etc.), alkylation ( alkylation), carboxylation, hydroxylation, glycation, biotinylation, ubiquitinylation, changes in chemical properties (e.g., beta-removal deimide And deamidation) and structural changes (eg, formation of disulfide bridges). In addition, it includes changes in amino acids, such as changes in amino groups, carboxyl groups, or side chains, caused by chemical reactions occurring in the process of bonding with crosslinkers to form peptide conjugates.

The peptides disclosed herein can be wild-type peptides that have been identified and isolated from native sources. Meanwhile, the peptide disclosed in the present specification may be an artificial variant comprising an amino acid sequence in which one or more amino acids have been substituted, deleted, and/or inserted compared to the peptides of SEQ ID NO: 1. Amino acid changes in wild-type polypeptides as well as in artificial variants include conservative amino acid substitutions that do not significantly affect the folding and/or activity of the protein. Examples of conservative substitutions include basic amino acids (arginine, lysine and histidine), acidic amino acids (glutamic acid and aspartic acid), polar amino acids (glutamine and asparagine), hydrophobic amino acids (leucine, isoleucine, valine and methionine), aromatic amino acids (phenylalanine, Tryptophan and tyrosine), and small amino acids (glycine, alanine, serine and threonine). In general, amino acid substitutions that do not alter a specific activity are known in the art. The most common exchanges are Ala/Ser, Val/Ile, Asp/Glu, Thr/Ser, Ala/Gly, Ala/Thr, Ser/Asn, Ala/Val, Ser/Gly, Tyr/Phe, Ala/Pro, Lys/Arg, Asp/Asn, Leu/Ile, Leu/Val, Ala/Glu, and Asp/Gly, and vice versa. Other examples of conservative substitution are shown in the following table.

Original amino acids Exemplary residue substitution Preferred residue substitution Ala (A) val; leu; ile Val Arg (R) lys; gln; asn Lys Asn (N) gln; his; asp, lys; arg Gln Asp (D) glu; asn Glu Cys (C) ser; ala Ser Gln (Q) asn; glu Asn Glu (E) asp; gln Asp Gly (G) Ala Ala His (H) asn; gln; lys; arg Arg Ile (I) leu; val; met; ala; phe; norleucine Leu Leu (L) norleucine; ile; val; met; ala; phe Ile Lys (K) arg; gln; asn Arg Met (M) leu; phe; ile Leu Phe (F) leu; val; ile; ala; tyr Tyr Pro (P) Ala Ala Ser (S) thr Thr Thr (T) Ser Ser Trp (W) tyr; phe Tyr Tyr (Y) trp; phe; thr; ser Phe Val (V) ile; leu; met; phe; ala; norleucine Leu

Substantial modifications in the biological properties of peptides include (a) their effect in maintaining the structure of the polypeptide backbone in the substitution region, e.g., a sheet or helical conformation, and (b) the charge of the molecule at the target site. Alternatively, their effect in maintaining hydrophobicity, or (c) their effect in maintaining the bulk of the side chain, is performed by selecting a substituent that differs considerably. Natural residues are divided into the following groups based on their usual side chain properties:

(1) hydrophobicity: norleucine, met, ala, val, leu, ile;

(2) neutral hydrophilicity: cys, ser, thr;

(3) acidic: asp, glu;

(4) basic: asn, gln, his, lys, arg;

(5) residues that influence chain orientation: gly, pro; And

(6) aromatic: trp, tyr, phe.

Non-conservative substitutions will be made by exchanging a member of one of these classes for another class. Any cysteine residue not related to maintaining the proper conformational structure of the peptide can generally be substituted with serine to improve the oxidative stability of the molecule and prevent abnormal crosslinking. Conversely, cysteine bond(s) can be added to the peptide to improve its stability.

Another type of amino acid variant of the peptide is a change in the glycosylation pattern of the antibody. The meaning of change refers to the deletion of one or more carbohydrate moieties found in the peptide and/or the addition of one or more glycosylation sites that are not present in the peptide.

Glycosylation of peptides is typically N-linked or O-linked. N-linked refers to that a carbohydrate moiety is attached to the side chain of an asparagine moiety. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are recognition sequences for enzymatic attachment of carbohydrate residues to the asparagine side chain. Thus, the presence of one of these tripeptide sequences in the polypeptide creates a potential glycosylation site. O-linked glycosylation means attaching one of the sugars N-acetylgalactosamine, galactose or xylose to a hydroxyamino acid, most commonly serine or threonine, but 5-hydroxyproline or 5-hydroxylysine You can also use

The addition of the glycosylation site to the peptide is conveniently carried out by changing the amino acid sequence to contain one or more of the aforementioned tripeptide sequences (for N-linked glycosylation sites). These changes may also be made by adding or substituting one or more serine or threonine residues to the sequence of the original antibody (for O-linked glycosylation sites).

A peptide having the sequence of SEQ ID NO: 1, a fragment of the sequence of SEQ ID NO: 1, or a peptide having a sequence homology of 80% or more with the peptide sequence according to an aspect of the present invention has low toxicity in cells and high stability in vivo. Has an advantage. SEQ ID NO: 1 in the present invention is a telomerase-derived peptide, which is a peptide consisting of 16 amino acids as follows.

SEQ ID NO: 1: EARPALLTSRLRFIPK

In one aspect of the present invention, a composition for inhibiting keloids comprising a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a peptide that is a fragment thereof as an active ingredient to provide.

The composition for inhibiting keloids according to one aspect of the present invention comprises a peptide comprising the amino acid sequence of SEQ ID NO: 1 on one side, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a peptide that is a fragment thereof. It may be included in an amount of µg/mg to 1 mg/mg, specifically 1 µg/mg to 0.5 mg/mg, and more specifically 10 µg/mg to 0.1 mg/mg. When included in the above range, not only the present invention is appropriate to exhibit the intended effect, but also the stability and safety of the composition for inhibiting keloids may be satisfied, and it may be appropriate to include in the above range in terms of cost-effectiveness.

The composition for inhibiting keloids according to an aspect of the present invention can be applied to all animals including humans, dogs, chickens, pigs, cows, sheep, guinea pigs or monkeys.

In one aspect of the present invention, the composition comprises a peptide comprising the amino acid sequence of SEQ ID NO: 1, a peptide having a sequence homology of 80% or more with the amino acid sequence, or a peptide that is a fragment thereof as an active ingredient. The composition is provided.

The terms used in the present specification are intended only for the purpose of describing specific embodiments, and are not intended to limit the present invention. The term in which the number is omitted before the noun is not intended to limit the quantity, but rather indicates the existence of one or more of the mentioned noun items. The terms “comprising”, “having”, and “including” are interpreted as open terms (ie, meaning “including but not limited to”).

References to a range of values are merely in lieu of referring individually to each individual number falling within that range, and unless otherwise stated, each number applies to the specification as if it were individually stated in the specification. do. Limit values of all ranges are included within that range and can be combined independently.

All methods mentioned herein may be performed in any suitable order unless otherwise specified or clearly contradicted by context. The use of any one and all embodiments or exemplary language (e.g., "such as") is only intended to better describe the invention and, unless included in the claims, is intended to limit the scope of the invention. I am not trying to limit it. No language in the specification should be construed as essential to the practice of the present invention with any unclaimed element. Unless otherwise defined, technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art to which the present invention belongs.

Preferred embodiments of the invention include the most optimal mode known to the inventor for carrying out the invention. Variations of the preferred embodiments may become apparent to those skilled in the art upon reading the preceding description. The inventors expect those skilled in the art to make appropriate use of such variations, and the inventors expect the invention to be practiced in a manner different from that described herein. Accordingly, the present invention includes equivalents and all variations of the subject matter of the invention mentioned in the appended claims, as permitted by the patent law. Moreover, within all possible variations, any combination of the above-mentioned components is included in the present invention unless otherwise indicated herein or clearly contradicted by context. While the present invention has been specifically shown and described with reference to exemplary embodiments, those skilled in the art will appreciate that various changes may be made in form and detail without departing from the spirit and scope of the invention as defined by the following claims.

In the following examples, the peptide (PEP 1) having the sequence set forth in SEQ ID NO: 1 and a composition comprising the same were intended to confirm the effect of inhibiting keloid growth.

Hereinafter, the configuration and effects of the present invention will be described in more detail with reference to examples and experimental examples. However, the following examples and experimental examples are provided only for purposes of illustration to aid understanding of the present invention, and the scope and scope of the present invention are not limited thereto.

Example 1: Synthesis of Peptide

The peptide of SEQ ID NO: 1 (hereinafter referred to as "PEP 1") was prepared according to a known solid-phase peptide synthesis method. Specifically, the peptides were synthesized by coupling amino acids one by one from the C-terminus through the Fmoc solid phase peptide synthesis (SPPS) using ASP48S (Peptron, Inc., Daejeon, Korea). As follows, the first amino acid of the C-terminus of the peptides attached to the resin was used. For example:

NH2-Lys(Boc)-2-chloro-Trityl Resin

NH2-Ala-2-chloro-Trityl Resin

NH2-Arg(Pbf)-2-chloro-Trityl Resin

All amino acid raw materials used for peptide synthesis are Trt, Boc, t-Bu (t-butylester), Pbf (2,2,4,6, in which the N-term is protected with Fmoc and all residues are removed from acid). 7-pentamethyl dihydro-benzofuran-5-sulfonyl) and the like were used. For example:

Fmoc-Ala-OH, Fmoc-Arg(Pbf)-OH, Fmoc-Glu(OtBu)-OH, Fmoc-Pro-OH, Fmoc-Leu-OH, Fmoc-Ile-OH, Fmoc-Phe-OH, Fmoc- Ser(tBu)-OH, Fmoc-Thr(tBu)-OH, Fmoc-Lys(Boc)-OH, Fmoc-Gln(Trt)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Met-OH, Fmoc -Asn(Trt)-OH, Fmoc-Tyr(tBu)-OH, Fmoc-Ahx-OH, Trt-Mercaptoacetic acid.

HBTU[2-(1H-Benzotriazole-1-yl)-1,1,3,3-tetamethylaminium hexafluorophosphate] / HOBt [N-Hydroxxybenzotriazole] /NMM [4-Methylmorpholine] is used as the coupling reagent. I did. Fmoc removal was performed using piperidine in DMF of 20%. Cleavage Cocktail [TFA (trifluoroacetic acid) / TIS (triisopropylsilane) / EDT (ethanedithiol) / H2O = 92.5/2.5/2.5/2.5] was used to separate the synthesized peptide from the resin and remove the protecting group from the residue.

Each peptide was synthesized by reacting each of the amino acids to the starting amino acid to which the amino acid protecting group was bound to the solid support, washing with a solvent, and repeating the process of deprotection. The synthesized peptide was cleaved from the resin and purified by HPLC, and the synthesis was confirmed by MS and freeze-dried.

As a result of high performance liquid chromatography on the peptides used in this example, the purity of all peptides was 95% or higher.

A detailed process for preparing the peptide PEP 1 will be described as follows.

1) coupling

After dissolving the amino acid protected in NH2-Lys(Boc)-2-chloro-Trityl Resin (8 equivalents) and coupling reagent HBTU (8 equivalents)/HOBt (8 equivalents)/NMM (16 equivalents) in DMF, The reaction was performed at room temperature for 2 hours, followed by washing with DMF, MeOH, and DMF.

2) Fmoc deprotection

Piperidine (piperidine in DMF) was added in 20% DMF, reacted twice for 5 minutes at room temperature, and washed in the order of DMF, MeOH, and DMF.

3) Peptide basic skeleton NH2-E(OtBu)-AR(Pbf)-PALLT(tBu)-S(tBu)-R(Pbf)LR(Pbf)-FIPK(Boc)- by repeating reactions 1 and 2 2-chloro-Trityl Resin).

4) Cleavage: Cleavage Cocktail was added to the synthesized peptide resin, reacted for 5 minutes, and this was repeated twice to separate the peptide from the resin.

5) After adding cooling diethyl ether to the obtained mixture, the peptide obtained by centrifugation was precipitated.

6) After purification by Prep-HPLC, the molecular weight was confirmed by LC/MS and frozen to prepare a powder.

Example 2: Effect of PEP 1 on inhibiting keloid proliferation

Experimental Example 1: Cell Growth Curve Measurement

Cell growth curve was measured to confirm the effect of PEP 1 on inhibiting cell proliferation. The specific method of measurement is as follows.

HaCaT cells were divided into two groups (a medium containing a general medium and a medium containing 40 μM of PEP 1) and cultured for about 3 weeks. The culture was cultured using a T75 flask, and the culture solution was replaced every 2 days. To measure the number of cells in culture (cell counting (triplicate experiments)), a trypan blue dye exclusion assay was used.

1 is a graph showing a relative ratio of cell proliferation changes in a group treated with PEP 1 when the growth of a group cultured with a medium is 1. The specific formula for calculating the ratio is as follows.

Total cell number of media added PEP1 cultured in the presence of PEP 1/Media total cell number of control group cultured under normal conditions

Figure 1 shows that PEP 1 has the effect of inhibiting the proliferation of HaCaT cells, which

It shows that PEP 1 can be used as a keloid treatment.

Experimental Example 2: Scratch Assay

Of PEP 1 In order to measure the keloid inhibitory efficacy, a scratch assay was performed as follows.

6 Inject 5x10 ⁵ HaCaT cells for each micro into a micro cell culture plate (seeding), stabilize it overnight and incubate with 90% or more confluence, and then sterilized 200 μl pipette tip ( tip) Using the front part, the central part of the smile was scratched vertically once and wounded. Thereafter, the control medium and the PEP 1 40 μM treatment group were divided into two groups, followed immediately (after 0 hours), 12 hours, 36 hours, and 52 hours, and observed under a microscope.

As a result of the experiment, in the PEP 1 (40 μM) treatment group, it was observed that the scratched portion is refilled with cells than in the control group. This indicates that PEP 1 has an effect of inhibiting the growth of keratinocytes, that is, an effect of inhibiting keloid proliferation. In conclusion, it means that PEP 1 can be used as a composition for inhibiting keloids.

<110> KAEL-GEMVAX CO., LTD. KIM, Sangjae <120> Composition and Method for Inhibiting Keloid <130> 14P295/IND <160> 2 <170> PatentIn version 3.2 <210> 1 <211> 16 <212> PRT <213> Homo sapiens <400> 1 Glu Ala Arg Pro Ala Leu Leu Thr Ser Arg Leu Arg Phe Ile Pro Lys 1 5 10 15 <210> 2 <211> 1132 <212> PRT <213> Homo sapiens <400> 2 Met Pro Arg Ala Pro Arg Cys Arg Ala Val Arg Ser Leu Leu Arg Ser 1 5 10 15 His Tyr Arg Glu Val Leu Pro Leu Ala Thr Phe Val Arg Arg Leu Gly 20 25 30 Pro Gln Gly Trp Arg Leu Val Gln Arg Gly Asp Pro Ala Ala Phe Arg 35 40 45 Ala Leu Val Ala Gln Cys Leu Val Cys Val Pro Trp Asp Ala Arg Pro 50 55 60 Pro Pro Ala Ala Pro Ser Phe Arg Gln Val Ser Cys Leu Lys Glu Leu 65 70 75 80 Val Ala Arg Val Leu Gln Arg Leu Cys Glu Arg Gly Ala Lys Asn Val 85 90 95 Leu Ala Phe Gly Phe Ala Leu Leu Asp Gly Ala Arg Gly Gly Pro Pro 100 105 110 Glu Ala Phe Thr Thr Ser Val Arg Ser Tyr Leu Pro Asn Thr Val Thr 115 120 125 Asp Ala Leu Arg Gly Ser Gly Ala Trp Gly Leu Leu Leu Arg Arg Val 130 135 140 Gly Asp Asp Val Leu Val His Leu Leu Ala Arg Cys Ala Leu Phe Val 145 150 155 160 Leu Val Ala Pro Ser Cys Ala Tyr Gln Val Cys Gly Pro Pro Leu Tyr 165 170 175 Gln Leu Gly Ala Ala Thr Gln Ala Arg Pro Pro Pro His Ala Ser Gly 180 185 190 Pro Arg Arg Arg Leu Gly Cys Glu Arg Ala Trp Asn His Ser Val Arg 195 200 205 Glu Ala Gly Val Pro Leu Gly Leu Pro Ala Pro Gly Ala Arg Arg Arg 210 215 220 Gly Gly Ser Ala Ser Arg Ser Leu Pro Leu Pro Lys Arg Pro Arg Arg 225 230 235 240 Gly Ala Ala Pro Glu Pro Glu Arg Thr Pro Val Gly Gln Gly Ser Trp 245 250 255 Ala His Pro Gly Arg Thr Arg Gly Pro Ser Asp Arg Gly Phe Cys Val 260 265 270 Val Ser Pro Ala Arg Pro Ala Glu Glu Ala Thr Ser Leu Glu Gly Ala 275 280 285 Leu Ser Gly Thr Arg His Ser His Pro Ser Val Gly Arg Gln His His 290 295 300 Ala Gly Pro Pro Ser Thr Ser Arg Pro Pro Arg Pro Trp Asp Thr Pro 305 310 315 320 Cys Pro Pro Val Tyr Ala Glu Thr Lys His Phe Leu Tyr Ser Ser Gly 325 330 335 Asp Lys Glu Gln Leu Arg Pro Ser Phe Leu Leu Ser Ser Leu Arg Pro 340 345 350 Ser Leu Thr Gly Ala Arg Arg Leu Val Glu Thr Ile Phe Leu Gly Ser 355 360 365 Arg Pro Trp Met Pro Gly Thr Pro Arg Arg Leu Pro Arg Leu Pro Gln 370 375 380 Arg Tyr Trp Gln Met Arg Pro Leu Phe Leu Glu Leu Leu Gly Asn His 385 390 395 400 Ala Gln Cys Pro Tyr Gly Val Leu Leu Lys Thr His Cys Pro Leu Arg 405 410 415 Ala Ala Val Thr Pro Ala Ala Gly Val Cys Ala Arg Glu Lys Pro Gln 420 425 430 Gly Ser Val Ala Ala Pro Glu Glu Glu Asp Thr Asp Pro Arg Arg Leu 435 440 445 Val Gln Leu Leu Arg Gln His Ser Ser Pro Trp Gln Val Tyr Gly Phe 450 455 460 Val Arg Ala Cys Leu Arg Arg Leu Val Pro Pro Gly Leu Trp Gly Ser 465 470 475 480 Arg His Asn Glu Arg Arg Phe Leu Arg Asn Thr Lys Lys Phe Ile Ser 485 490 495 Leu Gly Lys His Ala Lys Leu Ser Leu Gln Glu Leu Thr Trp Lys Met 500 505 510 Ser Val Arg Asp Cys Ala Trp Leu Arg Arg Ser Pro Gly Val Gly Cys 515 520 525 Val Pro Ala Ala Glu His Arg Leu Arg Glu Glu Ile Leu Ala Lys Phe 530 535 540 Leu His Trp Leu Met Ser Val Tyr Val Val Glu Leu Leu Arg Ser Phe 545 550 555 560 Phe Tyr Val Thr Glu Thr Thr Phe Gln Lys Asn Arg Leu Phe Phe Tyr 565 570 575 Arg Lys Ser Val Trp Ser Lys Leu Gln Ser Ile Gly Ile Arg Gln His 580 585 590 Leu Lys Arg Val Gln Leu Arg Glu Leu Ser Glu Ala Glu Val Arg Gln 595 600 605 His Arg Glu Ala Arg Pro Ala Leu Leu Thr Ser Arg Leu Arg Phe Ile 610 615 620 Pro Lys Pro Asp Gly Leu Arg Pro Ile Val Asn Met Asp Tyr Val Val 625 630 635 640 Gly Ala Arg Thr Phe Arg Arg Glu Lys Arg Ala Glu Arg Leu Thr Ser 645 650 655 Arg Val Lys Ala Leu Phe Ser Val Leu Asn Tyr Glu Arg Ala Arg Arg 660 665 670 Pro Gly Leu Leu Gly Ala Ser Val Leu Gly Leu Asp Asp Ile His Arg 675 680 685 Ala Trp Arg Thr Phe Val Leu Arg Val Arg Ala Gln Asp Pro Pro Pro 690 695 700 Glu Leu Tyr Phe Val Lys Val Asp Val Thr Gly Ala Tyr Asp Thr Ile 705 710 715 720 Pro Gln Asp Arg Leu Thr Glu Val Ile Ala Ser Ile Ile Lys Pro Gln 725 730 735 Asn Thr Tyr Cys Val Arg Arg Tyr Ala Val Val Gln Lys Ala Ala His 740 745 750 Gly His Val Arg Lys Ala Phe Lys Ser His Val Ser Thr Leu Thr Asp 755 760 765 Leu Gln Pro Tyr Met Arg Gln Phe Val Ala His Leu Gln Glu Thr Ser 770 775 780 Pro Leu Arg Asp Ala Val Val Ile Glu Gln Ser Ser Ser Leu Asn Glu 785 790 795 800 Ala Ser Ser Gly Leu Phe Asp Val Phe Leu Arg Phe Met Cys His His 805 810 815 Ala Val Arg Ile Arg Gly Lys Ser Tyr Val Gln Cys Gln Gly Ile Pro 820 825 830 Gln Gly Ser Ile Leu Ser Thr Leu Leu Cys Ser Leu Cys Tyr Gly Asp 835 840 845 Met Glu Asn Lys Leu Phe Ala Gly Ile Arg Arg Asp Gly Leu Leu Leu 850 855 860 Arg Leu Val Asp Asp Phe Leu Leu Val Thr Pro His Leu Thr His Ala 865 870 875 880 Lys Thr Phe Leu Arg Thr Leu Val Arg Gly Val Pro Glu Tyr Gly Cys 885 890 895 Val Val Asn Leu Arg Lys Thr Val Val Asn Phe Pro Val Glu Asp Glu 900 905 910 Ala Leu Gly Gly Thr Ala Phe Val Gln Met Pro Ala His Gly Leu Phe 915 920 925 Pro Trp Cys Gly Leu Leu Leu Asp Thr Arg Thr Leu Glu Val Gln Ser 930 935 940 Asp Tyr Ser Ser Tyr Ala Arg Thr Ser Ile Arg Ala Ser Leu Thr Phe 945 950 955 960 Asn Arg Gly Phe Lys Ala Gly Arg Asn Met Arg Arg Lys Leu Phe Gly 965 970 975 Val Leu Arg Leu Lys Cys His Ser Leu Phe Leu Asp Leu Gln Val Asn 980 985 990 Ser Leu Gln Thr Val Cys Thr Asn Ile Tyr Lys Ile Leu Leu Leu Gln 995 1000 1005 Ala Tyr Arg Phe His Ala Cys Val Leu Gln Leu Pro Phe His Gln Gln 1010 1015 1020 Val Trp Lys Asn Pro Thr Phe Phe Leu Arg Val Ile Ser Asp Thr Ala 1025 1030 1035 1040 Ser Leu Cys Tyr Ser Ile Leu Lys Ala Lys Asn Ala Gly Met Ser Leu 1045 1050 1055 Gly Ala Lys Gly Ala Ala Gly Pro Leu Pro Ser Glu Ala Val Gln Trp 1060 1065 1070 Leu Cys His Gln Ala Phe Leu Leu Lys Leu Thr Arg His Arg Val Thr 1075 1080 1085 Tyr Val Pro Leu Leu Gly Ser Leu Arg Thr Ala Gln Thr Gln Leu Ser 1090 1095 1100 Arg Lys Leu Pro Gly Thr Thr Leu Thr Ala Leu Glu Ala Ala Ala Asn 1105 1110 1115 1120 Pro Ala Leu Pro Ser Asp Phe Lys Thr Ile Leu Asp 1125 1130

Claims (6)

A composition for inhibiting keloids, comprising a peptide consisting of the amino acid sequence of SEQ ID NO: 1, wherein the peptide is contained in an effective amount for inhibiting keloids. The method of claim 1. The composition is for administration to an individual in need of inhibiting the growth of keratinocytes, a composition for inhibiting keloids. The method of claim 1. The peptide is derived from human telomerase, the composition for inhibiting keloids. The composition for inhibiting keloids according to any one of claims 1 to 3; And a kit for suppressing keloids including instructions. delete delete

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