In silico designed botulinum toxin mimetic peptides that inhibit the release of neurotransmitters including acetylcholine, and their use in wrinkle improvement

Abstract

The present invention relates to a peptide that inhibits the secretion of neurotransmitters from cells, and provides a composition and kit for skin whitening or wrinkle reduction, and a method for skin whitening or wrinkle reduction, each containing the peptide as an active ingredient. The peptide is characterized by having cell permeability without being fused to a protein transport domain such as a cell-penetrating peptide, and having an efficient skin whitening or wrinkle reduction effect.

Description

[Technical Field]

[0001] The present invention relates to peptides that inhibit the secretion of neurotransmitters from cells, and uses thereof. [Background technology]

[0002] The SNARE complex, which includes SNAP-25, syntaxin, and VAMP2, is involved in neurotransmitter export. Neurotransmitter export from the synapse involves the fusion of synaptic vesicles with the neuronal plasma membrane and requires various proteins that act together to form the synaptic fusion complex. These proteins, called SNARE proteins, include SNAP-25, syntaxin, and synaptobrevin. Synaptobrevin is also known as VAMP2. VAMP2 is located in the synaptic vesicle membrane, while SNAP-25 and syntaxin are associated with the plasma membrane. Calcium extrusion triggers the formation of a complex that draws the synaptic vesicle closer to the plasma membrane, allowing the membranes to fuse. This fusion allows the neurotransmitter contained in the vesicle to be exported into the synapse. Neurotransmitters include dopamine, acetylcholine, and norepinephrine. There is still a need for VAMP2-derived peptides that can efficiently inhibit the formation of SNARE complexes, but such SNARE proteins have the disadvantage that they cannot act efficiently on the skin due to the skin's protective function.

[0003] On the other hand, in order to move therapeutic drugs or proteins into cells, we are attempting to deliver drugs into cells using peptides that function as carriers that can transport target proteins into cells.

[0004] However, there is a need for peptides that have cell permeability even without being fused to such protein transduction domains. Summary of the Invention [Problem to be solved by the invention]

[0005] One aspect provides a peptide or a pharmaceutically acceptable salt thereof that inhibits secretion of a neurotransmitter from a neuron.

[0006] Another aspect provides polynucleotides encoding the peptides and vectors and host cells containing same.

[0007] Another embodiment provides a composition or kit comprising the peptide for use in skin whitening or wrinkle reduction.

[0008] Another embodiment provides a method for whitening the skin or improving wrinkles in an individual by administering the peptide to the individual. [Means for solving the problem]

[0009] One embodiment provides a peptide or a pharmaceutically acceptable salt thereof that inhibits the secretion of a neurotransmitter from a nerve cell, the peptide having the amino acid sequence of SEQ ID NO:1.

[0010] The amino acids of the peptide are D- or L-amino acids. The N-terminus or C-terminus of the peptide is modified. The modification is a chemical modification. The modification improves the stability or delivery of the peptide. The modification does not substantially reduce the physiological activity of the peptide. For example, the N-terminus of the peptide is bound to any one protecting group selected from the group consisting of an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, a butoxycarbonyl group, an allyloxycarbonyl group, and polyethylene glycol (PEG). For example, the C-terminus of the peptide is bound to any one protecting group selected from the group consisting of an amino group (-NH), a tertiary alkyl group, and an azide (-NHNH). The modification includes esterification of the carboxyl groups of glutamic acid and aspartic acid. The modification removes the negative charge of the amino acid and increases its hydrophobicity. The modified peptide can thereby improve its bioavailability, including stability and fat solubility, and can easily pass through the blood-brain barrier and / or epithelial tissue. The N-terminus of the peptide is acetylated. The C-terminus of the peptide is aminated. The modification is hydrolyzed in the body by intracellular esterases, etc.

[0011] The peptide inhibits the formation of a SNARE complex containing SNAP-25, syntaxin, and VAMP2, thereby suppressing neurotransmitter release. The SNARE complex, for example, contains SNAP-25, syntaxin 1a, and VAMP2. Neurotransmitter release from synapses is associated with the fusion of synaptic vesicles with the neuronal plasma membrane and requires various proteins that function together to form a synaptic fusion complex. These proteins, known as SNARE proteins, include SNAP-25, syntaxin, and synaptobrevin. Synaptobrevin is also known as VAMP2. VAMP2 is located in the synaptic vesicle membrane, while SNAP-25 and syntaxin are associated with the plasma membrane. Calcium release triggers the formation of a complex, drawing the synaptic vesicle closer to the plasma membrane and fusing the membrane. This fusion allows the neurotransmitter contained in the vesicle to be released into the synapse. The neurotransmitter may be any neurotransmitter released through a synapse. The neurotransmitter may be dopamine, acetylcholine, epinephrine, norepinethrine, serotonin, histamine, glutamate, glycine, gamma-aminobutyric acid, or a combination thereof. The neurotransmitter may be, for example, dopamine, acetylcholine, or a combination thereof. The peptide mimics VAMP2 to inhibit the formation of the SNARE complex, thereby suppressing the release of neurotransmitters into synapses. Thus, the peptide can attenuate or ameliorate various symptoms caused by the release of neurotransmitters into synapses. The peptide can prevent or treat various symptoms caused by the release of neurotransmitters into synapses. The symptoms include blepharospasm, facial spasm, hemifacial spasm, strabismus, urinary incontinence, frequent urination, equinus deformity due to childhood cerebral palsy, hyperhidrosis, headache, migraine, upper limb muscle stiffness, intermuscular spasm, spasmodic torticollis, anal fissure, cerebral palsy, temporomandibular joint disorder, neuralgia, muscle pain, or dystonia. The peptide can whiten skin or improve wrinkles.The peptides may also be used to improve or treat neuronal exocytosis-mediated conditions, such as spasticailments, including dystonias, strabismus, tics, blepharospasm, or facial scoliosis.

[0012] The peptides can be obtained by classical solid-phase chemical peptide synthesis. Alternatively, the peptides can be obtained by recombinant DNA technology. For example, the method includes inserting a polynucleotide encoding the peptide into a suitable plasmid or vector, introducing the vector into a host cell, culturing the resulting cells to form the peptide in the culture, and selectively purifying the peptide.

[0013] The peptide may or may not be fused to a cell membrane-penetrating peptide, which increases the passage of the fused peptide through the cell membrane. The cell membrane-penetrating peptide is selected from the group consisting of TD1, IMT-P8, Transkin, VP2-2, RBD-1, SN25-2, STX-1, and TDb-1.

[0014] As used herein, the peptide is understood to include not only the peptide but also its salts, which are pharmaceutically or cosmetically acceptable salts of the peptide.

[0015] Another embodiment provides a composition for skin whitening or wrinkle reduction, comprising the peptide as an active ingredient.

[0016] The composition further comprises a pharmaceutically or cosmetically acceptable carrier. The carrier is a diluent or excipient. The carrier is an antioxidant, stabilizer, solubilizer, vitamin, pigment, fragrance, etc. The diluent is water, a buffer, or saline.

[0017] The composition may also further comprise a pharmaceutically or cosmetically acceptable adjuvant.

[0018] The composition may be a cosmetic, pharmaceutical, or food composition, and may be any formulation, such as a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant-containing cleansing oil, powder foundation, emulsion foundation, wax foundation, or spray.

[0019] When the formulation is a paste, cream or gel, the carrier component may comprise one or more of vegetable oils, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silica, talc and zinc oxide.

[0020] When the formulation is a powder or spray, the carrier is one or more of lactose, talc, silica, aluminum hydroxide, calcium silicate, and polyamide powder. In particular, when the formulation is a spray, the composition further comprises a propellant such as chlorofluorohydrocarbon, propane / butane, and dimethyl ether.

[0021] When the formulation is a solution or emulsion, the carrier includes one or more of a solvent, a solubilizer, and an emulsifier, such as one or more of ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butyl glycol oil, aliphatic esters of glycerol, polyethylene glycol, and fatty acid esters of sorbitan.

[0022] When the formulation is a suspension, the carrier is one or more of a liquid diluent such as water, ethanol, and propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol esters, and polyoxyethylene sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar, or tragacanth.

[0023] The content of the peptide may be an amount effective for skin whitening or wrinkle reduction, for example, 0.001 to 95.0%, 0.001 to 70.0%, 0.001 to 50.0%, or 0.01 to 50.0% by weight of the composition.

[0024] Another embodiment provides a kit for skin whitening or wrinkle improvement, comprising the peptide.

[0025] The kit further includes at least one selected from the group consisting of a carrier and an adjuvant, and instructions describing how to use the peptide for skin whitening or wrinkle reduction.

[0026] Another embodiment provides a method for whitening or improving the appearance of wrinkles in an individual, comprising administering to the individual an amount of the peptide effective to whiten or improve the appearance of wrinkles.

[0027] The peptide is in the form of itself or in the form of a composition. The administration is via any route. The administration is oral or parenteral. The administration is applied to the nasal cavity, mucous membrane, or skin. The individual is a human or a non-human animal, e.g., a mammal. The method can be a cosmetic method.

[0028] Another aspect provides a polynucleotide encoding the peptide.

[0029] Another aspect provides a vector containing the polynucleotide. The vector may be any vector that can be used to deliver the polynucleotide. The vector may be a nucleic acid construct, a plasmid, or a virus-derived vector. The vector may be an expression vector, for example, an expression vector that can be expressed in a mammal.

[0030] Another aspect provides a recombinant host cell containing the polynucleotide. The host cell may be a bacterium or an animal cell. The animal cell may be a well-known animal cell, such as a Chinese hamster ovary cell (CHO).

[0031] Another aspect provides a composition for use in inhibiting the formation of a SNARE complex containing SNAP-25, syntaxin, and VAMP2, comprising the peptide as an active ingredient. The composition further comprises a carrier or adjuvant. The composition may be a cosmetic, pharmaceutical, or food composition.

[0032] The composition is for improving or treating a neuron-exocytosis-mediated condition, such as blepharospasm, facial spasm, hemifacial spasm, strabismus, urinary incontinence, frequent urination, equinus deformity due to childhood cerebral palsy, hyperhidrosis, headache, migraine, upper limb muscle stiffness, intermuscular spasms, spasmodic torticollis, anal fissures, cerebral palsy, temporomandibular joint disorder, neuralgia, myalgia, or dystonia. The condition is a muscle tension disorder, such as dystonias, strabismus, tics, blepharospasm, or facial scoliosis.

[0033] The content of the peptide and the carrier or adjuvant are as described above.

[0034] Another embodiment provides a kit for use in inhibiting the formation of a SNARE complex containing SNAP-25, syntaxin, and VAMP2, comprising the peptide, the kit further comprising one or more of a carrier and an adjuvant.

[0035] Another embodiment provides a method for inhibiting formation of a SNARE complex in an individual, comprising administering to the individual the peptide.

[0036] The method is for ameliorating or treating a neuron-exocytosis-mediated condition, such as blepharospasm, facial spasm, hemifacial spasm, strabismus, urinary incontinence, frequent urination, equinus deformity due to childhood cerebral palsy, hyperhidrosis, headache, migraine, upper limb muscle stiffness, grand muscular spasms, spasmodic torticollis, anal fissures, cerebral palsy, temporomandibular joint disorder, neuralgia, myalgia, or dystonia. The condition is a muscle tension disorder, such as dystonias, strabismus, tics, blepharospasm, or facial scoliosis.

[0037] The peptide may be in the form of a peptide or a composition comprising the same. The amount of the peptide administered is an amount effective to inhibit the formation of a SNARE complex in an individual. [Effects of the Invention]

[0038] The peptide according to one embodiment can be used for skin whitening or wrinkle reduction.

[0039] According to one embodiment, a polynucleotide encoding the peptide, a vector containing the same, and a host cell can be used to produce the peptide.

[0040] According to one embodiment, a composition or kit comprising the peptide can be used for skin whitening or wrinkle reduction, or for improving or treating neuron exocytosis-mediated conditions.

[0041] The method according to one embodiment can effectively lighten the skin or reduce wrinkles in an individual, or improve or treat neuron exocytosis-mediated conditions. [Brief explanation of the drawings]

[0042] [Figure 1] FIG. 1 shows the effect of the P631 peptide on dopamine secretion from PC12 cells. [Figure 2] FIG. 1 shows the effect of the P631 peptide on acetylcholine secretion from PC12 cells. [Figure 3] FIG. 1 shows the results of an experiment on the cytotoxicity of the P631 peptide. [Figure 4] FIG. 1 shows the results of measuring the effect of the P631 peptide on skin irritation. [Figure 5] The cells were cultured in the presence of FITC-P631 (red) or FITC-control peptide (black), and the absorbance was measured at 470 nm, which corresponds to FITC emission. DETAILED DESCRIPTION OF THE INVENTION

[0043] The present invention will be described in more detail with reference to the following examples, but these examples are for illustrative purposes only and are not intended to limit the scope of the present invention.

[0044] Example 1: Selection of peptides capable of inhibiting neurotransmitter secretion and confirmation of their efficacy When SNARE complexes are formed in nerve cells, neurotransmitters such as acetylcholine are released outside the cell and bind to receptors in muscle cells, transmitting stimuli. This stimuli causes muscle cell contraction, resulting in facial wrinkles. Preventing the formation of SNARE complexes can prevent muscle contraction and eliminate wrinkles. For example, botulinum toxin is known to prevent the formation of SNARE complexes, preventing muscle contraction and eliminating wrinkles. Botulinum toxin cuts out specific regions of the proteins that make up the SNARE complex, preventing normal complex formation. Therefore, inhibiting the formation of SNARE complexes using peptides can be shown to reduce wrinkles.

[0045] In this example, peptides that inhibit the formation of SNARE complexes were selected, and their efficacy in inhibiting neurotransmitter secretion, improving wrinkles, and whitening skin was confirmed.

[0046] 1. Synthesis of candidate peptides In this example, a polypeptide was synthesized in which the N-terminus was protected with an acetyl group and the C-terminus was protected with an amino group in the amino acid sequence of SEQ ID NO: 1. The amino acid sequence of SEQ ID NO: 1 was designed using an in silico model. This polypeptide is also referred to as "P631" hereinafter. This polypeptide was created by modifying a portion of the v-snare coiled-coil domain of VAMP2, a member of the SNARE complex, as a template. This polypeptide can penetrate neurons and regulate neurotransmitter release. This polypeptide was prepared by chemical synthesis and used for experiments. P631 was not linked to a separate cell-penetrating peptide.

[0047] 2. Measurement of neurotransmitter secretion inhibitory activity We investigated whether the P631 peptide inhibits the formation of SNARE complexes and inhibits the secretion of neurotransmitters, specifically dopamine and acetylcholine.

[0048] (1) Effect of P631 peptide on dopamine secretion from neurons PC12 cells (Korean Cell Line Bank) were cultured in RPMI 1640 medium containing 10% FBS and 50 mg / mL NGF (2.5S; Alomone Labs, N-100) on Matrigel-coated 48-well plates at 37°C for 7 days. They were then cultured in RPMI 1640 medium containing 5% FBS for an additional 3 days at 37°C. PC12 cells are a cell line derived from pheochromocytoma cells that developed in the adrenal medulla of rats. Because chromaffin cells, which secrete catecholamines in the adrenal medulla, are already differentiated and do not divide, culturable PC12 cells are often used to study pheochromocytoma cells.

[0049] After the culture was completed, RPMI 1640 medium alone (controls 1 and 2 in Figure 1) or RPMI 1640 containing 20 μM P631 peptide was added to the PC-12 cells and cultured for 2 hours at 37°C. The medium was then removed, and all wells were washed three times with Kreb's buffer containing low potassium ions (118 mM NaCl, 1.2 mM MgSO, 2.5 mM CaCl, 5 mM KCl, 24 mM NaHCO, 2 mM KHPO, and 11 mM dextrose, pH 7.4). Next, 0.1 mL / well of Kreb's buffer containing low potassium ions was added to the peptide-free non-depolarization group (control group 1 in Figure 1), and 0.1 mL / well of Kreb's buffer containing high potassium ions (56 mM NaCl, 1.2 mM MgSO, 2.5 mM CaCl, 68 mM KCl, 24 mM NaHCO, 2 mM KHPO, and 11 mM dextrose, pH 7.4) was added to the peptide-free depolarization group (control group 2 in Figure 1) and the P631 peptide-containing depolarization group (experimental group in Figure 1). Depolarization was induced by incubation at 37°C for 8 minutes. After depolarization, 0.315 mL of supernatant was collected from the cells and transferred to a new 48-well plate. ELISA was performed according to the instructions for the Dopamine ELISA kit (Abnova, KA1887) to measure the amount of dopamine secreted into the medium.

[0050] The results are shown in Figure 1. Figure 1 shows the effect of P631 peptide on dopamine secretion in PC12 cells. As shown in Figure 1, the dopamine secretion rates of the group not treated with peptide and undergoing depolarization, i.e., control group 2, and the group treated with P631 peptide and undergoing depolarization, i.e., the experimental group, were 100% and 11%, respectively. This indicates that P631 peptide inhibits dopamine secretion from depolarized neurons.

[0051] (2) Effect of P631 peptide on acetylcholine secretion from neurons PC12 cells (Korean Cell Line Bank) were cultured in Matrigel-coated 48-well plates in RPMI1640 medium containing 10% FBS and 50 mg / mL NGF (2.5S; Alomone Labs, N-100) at 37°C for 7 days.

[0052] After the culture was completed, RPMI 1640 medium alone (controls 1 and 2 in Figure 2) or RPMI 1640 containing 20 μM P631 peptide was added to the PC-12 cells and cultured for 2 hours at 37°C. The medium was then removed, and all wells were washed three times with Kreb's buffer containing low potassium ions (118 mM NaCl, 1.2 mM MgSO, 2.5 mM CaCl, 5 mM KCl, 24 mM NaHCO, 2 mM KHPO, and 11 mM dextrose, pH 7.4). Next, 0.1 mL / well of Kreb's buffer containing low potassium ions was added to the peptide-free non-depolarization group (control group 1 in Figure 2), and 0.1 mL / well of Kreb's buffer containing high potassium ions (56 mM NaCl, 1.2 mM MgSO, 2.5 mM CaCl, 68 mM KCl, 24 mM NaHCO, 2 mM KHPO, and 11 mM dextrose, pH 7.4) was added to the peptide-free depolarization group (control group 2 in Figure 2) and the P631 peptide-containing depolarization group (experimental group in Figure 2). Depolarization was induced by incubation at 37°C for 8 minutes. After depolarization, 0.07 mL of supernatant was collected from the cells and transferred to a new 48-well plate. ELISA was performed according to the instructions for the Acetylcholine ELISA kit (AAT Bioquest, 111403) to measure the amount of acetylcholine secreted into the medium.

[0053] The results are shown in Figure 2. Figure 2 shows the effect of P631 peptide on acetylcholine secretion in PC12 cells. As shown in Figure 2, the acetylcholine secretion rates of the group not treated with peptide and undergoing depolarization, i.e., control group 2, and the group treated with P631 peptide and undergoing depolarization, i.e., the experimental group, were 100% and 39%, respectively. This indicates that P631 peptide inhibits acetylcholine secretion from depolarized neurons.

[0054] 2. Confirmation of toxicity of P631 peptide (1) Toxicity test of raw material: MTT analysis Human dermal fibroblast (HDF) cells purchased from the Korea Cell Line Bank were cultured in a 96-well plate at 8 × 10 3 The cells were seeded at a concentration of 100 cells / well in 100 μL of DMEM medium containing 10% FBS and cultured for 24 hours. HDF cells are human fibroblasts. The P631 peptide was then diluted into DMEM medium at concentrations of 0, 1, 5, 10, 15, 20, 25, 30, 40, and 50 μM, and the cells were replaced with the DMEM medium and cultured for another 24 hours.

[0055] After 24 hours, 20 μL of MTT solution was added to the DMEM medium to achieve a final MTT concentration of 0.5 mg / mL. After adding MTT, the cells were cultured for 4 hours in 5% CO2 medium at 37°C. The plate was centrifuged at 1,000 rpm for 10 minutes, and the MTT solution was removed. Each well was washed twice with PBS, and 200 μL of DMSO was added to dissolve the formazan produced. The plate was placed in a Spectra MAX i3 instrument, and the absorbance of the sample in each well was measured at 590 nm.

[0056] The results are shown in Figure 3. Figure 3 shows the results of the cytotoxicity experiment of the P631 peptide. As shown in Figure 3, in the MTT assay, the P631 peptide showed a cell viability of approximately 80% or more up to 40 μM compared to the untreated group (0 μM), and showed no cytotoxicity at the experimental concentration of 20 μM.

[0057] (2) Skin irritation test Negative and positive control groups were created by evenly applying 1x PBS and 5% SDS to artificial skin (Neoderm®-ED) purchased from Tegoscience. For the experimental group, 20 μl of 20 μM P631 peptide was evenly applied. After 15 minutes of incubation at room temperature, the tissue was transferred to a 12-well culture plate and incubated at 37°C in 5% CO2 for 15 minutes. After incubation, the tissue was washed twice with PBS and transferred to a new 12-well culture plate for 42 hours. After incubation, 2 ml of 0.3 mg / ml MTT solution was added and the cells were incubated for 3 hours. The samples in each well of the plate were decolorized with 0.04 N HCl-isopropanol and then placed in a Spectra MAX i3. The absorbance of each sample in each well was measured at 580 nm.

[0058] The results are shown in Figure 4. Figure 4 shows the results of measuring the effect of the P631 peptide on skin irritation. As shown in Figure 4, the P631 peptide was non-irritating, with a cell viability of approximately 103.6%. Here, a cell viability of 50% or more compared to the negative control group was determined to be non-irritating.

[0059] 3. Cell Permeability Test The NTERA-2 cell line, purchased from the Korea Cell Line Bank, was differentiated into neuron-like cells. The NTERA-2 cell line is a pluripotent human embryonic carcinoma cell line. The differentiated cells were cultured in a 6-well plate at a density of 1.5 × 10 6The cells were seeded at a concentration of 1000 cells / well in 2 mL of DMEM / F12 medium containing FBS and B-27 and cultured for 24 hours. FITC was fused to the N-terminus of the P631 peptide and the native VAMP2 peptide. These peptides are referred to as "FITC-P631" and "FITC-control peptide," respectively. The existing medium in the 6-well plate was removed, and 2 mL of the two peptides, prepared at 20 μM each, was added to DMEM / F12 medium per well and cultured for 24 hours. After incubation, the existing medium was removed, and the cells were washed with DPBS. Next, the cells were detached using 0.25% trypsin-EDTA and DMEM / F12 medium. The cells were then lysed in DPBS (FACS buffer) supplemented with 2% FBS and subjected to FACS analysis.

[0060] Figure 5 shows the results of measuring absorbance at 470 nm, which corresponds to FITC emission, when cells were cultured in the presence of FITC-P631 (red) or FITC-control peptide (black). As shown in Figure 5, the polypeptide-FITC exhibited significantly higher fluorescence intensity than the scrambled peptide-FITC. The area marked "P2" was determined to represent cells in which FITC was detected. This indicates that the P631 peptide, unlike the control peptide, is able to penetrate cells more effectively. In Figure 5, the vertical axis represents the number of cells, and the horizontal axis represents the FITC intensity. P631-P1 represents P631.

[0061] Sequence information SEQ ID NO: 1 (P631): NRRLRLTAAKLLDLLAIFR SEQ ID NO: 2 - Control peptide (VAMP2 native peptide): NRRLQQTQAQVDEVVDIMR

Claims

1. A peptide that inhibits the secretion of neurotransmitters from nerve cells, said peptide having the amino acid sequence of SEQ ID NO:

1.

2. The peptide of claim 1 , which is not linked to a cell-penetrating peptide.

3. 2. The peptide of claim 1, wherein the N-terminus of the peptide is bound to any one protecting group selected from the group consisting of an acetyl group, a fluorenylmethoxycarbonyl group, a formyl group, a palmitoyl group, a myristyl group, a stearyl group, a butoxycarbonyl group, an allyloxycarbonyl group, and a polyethylene glycol (PEG).

4. The C-terminus of the peptide is an amino group (-NH ２ ), tertiary alkyl groups and azides (—NHNH ２ 2. The peptide of claim 1, wherein the peptide is bound to any one of the protecting groups selected from the group consisting of:

5. 2. The peptide of claim 1, wherein the neurotransmitter is dopamine, acetylcholine, epinephrine, norepinethrine, serotonin, histamine, glutamic acid, glycine, gamma aminobutyric acid, or a combination thereof.

6. A composition for skin whitening or wrinkle reduction, comprising the peptide according to any one of claims 1 to 5 as an active ingredient.

7. A kit for skin whitening or wrinkle reduction, comprising the peptide according to any one of claims 1 to 5.

8. 8. The kit of claim 7, further comprising one or more selected from the group consisting of a diluent, an excipient, a carrier, and an adjuvant.

9. A method for whitening or improving the appearance of wrinkles in an individual, comprising administering to the individual an amount of a peptide according to any one of claims 1 to 5 that is effective for whitening or improving the appearance of wrinkles.

10. The method according to claim 9, wherein the method is makeup application.

Images