Adipotide peptide is a synthetic peptidomimetic and an experimental proapoptotic compound known as FTPP (Fat-Targeted Proapoptotic Peptide). Peptidomimetics are synthetic molecules that may mimic a natural protein’s structural domain. Adipotide appears to bind to the protein receptor prohibitin, which is why it also bears the name Prohibitin-targeting peptide 1 (Prohibitin-TP01). By doing so, it has proapoptotic potential on adipose tissue, meaning that it may induce cell death in white fat cells. Animal studies suggest that by inducing targeted apoptosis, Adipotide peptide may induce fat loss and improvement in several metabolic parameters.

 

Adipotide Peptide Overview

Adipotide FTPP appears to act by binding to the receptors for 2 specific proteins, ANXA2 (annexin A2) and prohibitin. Either of these receptors is expressed in various cells, but immunohistochemical analysis suggests that they form specific ANXA2-prohibitin receptor systems in white fat tissue.^[1]

Research suggests that these receptors may play a role in regulating fatty acid transport in white adipose tissues.^[2] Inhibiting the ANXA2 protein may lead to hypertrophy of white adipose cells due to reduced uptake of fatty acids.

On the other hand, prohibitin is a multifunctional membrane-associated protein that is thought to regulate cell survival and growth. It may trigger apoptosis by shuttling from the cell’s membrane to its nucleus.

Adipotide peptide has a unique structure consisting of the amino-acid sequence GKGGRAKDC-GG-D(KLAKLAK)2. The 9 amino acid sequence CKGGRAKDC appears to bear a specific affinity to the ANXA2-prohibitin receptor system found in the blood vessels supporting white adipose cells.^[3] At the same time, (KLAKLAK)2 may disrupt mitochondrial membranes upon receptor-mediated cell internalization and induce programmed cell death.

As Adipotide peptide appears to bind to prohibitin in white adipose vasculature, it may trigger apoptosis and can result in the ablation of white fat cells.

According to research, Adipotide peptide and other similar peptidomimetics may potentially reduce subcutaneous and visceral fat and even target intra-organ fat, such as in fatty liver diseases.^[4]

 

Research on Adipotide Peptide

Adipotide peptide may hold potential for two major research focuses –  obesity and cancer. Regarding its metabolic potential and the potential to induce fat loss, the peptidomimetic has been tested in mice, rats, and rhesus monkeys. In obese rats, 28 days of Adipotide peptide exposure led to a 30% reduction in body weight.^[5] It also appeared to significantly suppress their appetite, even though the leptin levels of the animals plummeted. Furthermore, the energy expenditure of the animals was not apparently affected.

In another study, the researchers suggested that Adipotide peptide may have led to metabolic improvements as soon as the 3rd day of the study, even before there was a noticeable reduction in the body weight of the tested mice. Kim et al. concluded that Adipotide “rapidly and potently improved the glucose tolerance of obese mice in a weight- and food intake-independent manner.”^[6] The peptidomimetic appeared to have reduced triglyceride and insulin levels as well.

In obese rhesus monkeys, Adipotide peptide exposure may have caused white adipose tissue blood vessels to undergo targeted apoptosis.^[7] As a result, the tested animals lost weight and improved their insulin sensitivity within the first month of study. A significant decrease in white adipose tissue was noted by dual-energy x-ray absorptiometry and magnetic resonance imaging.

 

Adipotide Peptide and Prostate Cancer

The destruction of white fat may also have positive consequences for prostate cancer. This is suggested to be so, due to a high level of white fat that has been implicated as a critical contributing factor in poor prostate cancer outcomes.^[8]

Studied have attempted to examine the impact of Adipotide peptide exposure in research models of prostate cancer. The study evaluated the action of a single cycle of Adipotide peptide in research models of castrate-resistant prostate cancer. According to the study, the models were put through the entire study cycle, but the study was terminated before completion.^{[9, 10]}

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Staquicini FI, Cardó-Vila M, Kolonin MG, Trepel M, Edwards JK, Nunes DN, Sergeeva A, Efstathiou E, Sun J, Almeida NF, Tu SM, Botz GH, Wallace MJ, O’Connell DJ, Krajewski S, Gershenwald JE, Molldrem JJ, Flamm AL, Koivunen E, Pentz RD, Dias-Neto E, Setubal JC, Cahill DJ, Troncoso P, Do KA, Logothetis CJ, Sidman RL, Pasqualini R, Arap W. Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients. Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42. doi: 10.1073/pnas.1114503108. Epub 2011 Nov 2. PMID: 22049339; PMCID: PMC3219136.
2. Salameh A, Daquinag AC, Staquicini DI, An Z, Hajjar KA, Pasqualini R, Arap W, Kolonin MG. Prohibitin/annexin 2 interaction regulates fatty acid transport in adipose tissue. JCI Insight. 2016 Jul 7;1(10):e86351. doi: 10.1172/jci.insight.86351. PMID: 27468426; PMCID: PMC4959783.
3. Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med. 2004 Jun;10(6):625-32. doi: 10.1038/nm1048. Epub 2004 May 9. PMID: 15133506.
4. Hossen N, Kajimoto K, Akita H, Hyodo M, Harashima H. A comparative study between nanoparticle-targeted therapeutics and bioconjugates as obesity medication. J Control Release. 2013 Oct 28;171(2):104-12. doi: 10.1016/j.jconrel.2013.07.013. Epub 2013 Jul 18. PMID: 23871959.
5. Kim DH, Woods SC, Seeley RJ. Peptide designed to elicit apoptosis in adipose tissue endothelium reduces food intake and body weight. Diabetes. 2010 Apr;59(4):907-15. doi: 10.2337/db09-1141. Epub 2010 Jan 26. PMID: 20103704; PMCID: PMC2844838.
6. Kim DH, Sartor MA, Bain JR, Sandoval D, Stevens RD, Medvedovic M, Newgard CB, Woods SC, Seeley RJ. Rapid and weight-independent improvement of glucose tolerance induced by a peptide designed to elicit apoptosis in adipose tissue endothelium. Diabetes. 2012 Sep;61(9):2299-310. doi: 10.2337/db11-1579. Epub 2012 Jun 25. PMID: 22733798; PMCID: PMC3425411.
7. Barnhart KF, Christianson DR, Hanley PW, Driessen WH, Bernacky BJ, Baze WB, Wen S, Tian M, Ma J, Kolonin MG, Saha PK, Do KA, Hulvat JF, Gelovani JG, Chan L, Arap W, Pasqualini R. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys. Sci Transl Med. 2011 Nov 9;3(108):108ra112. doi: 10.1126/scitranslmed.3002621. PMID: 22072637; PMCID: PMC3666164.
8. Allott EH, Masko EM, Freedland SJ. Obesity and prostate cancer: weighing the evidence. Eur Urol. 2013 May;63(5):800-9. doi: 10.1016/j.eururo.2012.11.013. Epub 2012 Nov 15. PMID: 23219374; PMCID: PMC3597763.
9. Smith, T. L., Sidman, R. L., Arap, W., & Pasqualini, R. (2022). Targeting vascular zip codes: from combinatorial selection to drug prototypes. In The Vasculome (pp. 393-401). Academic Press.
10. ClinicalTrials.gov [Internet]. National Library of Medicine (US). 2010 Dec 17 – . Identifier NCT01262664, A First-in-Man, Phase I Evaluation of A Single Cycle of Prohibitin Targeting Peptide 1 in Patients With Metastatic Prostate Cancer and Obesity; 2019 Jan 4; http://clinicaltrials.gov/ct2/show/NCT01262664

Vialox peptide (also known as Pentapeptide-3V) has been suggested to exhibit potential in preventing muscle contraction by exhibiting a curare-like effect at the neuromuscular junction, disallowing the nervous system signals from reaching the muscles. Vialox peptide is of interest because of its potential to communicate between muscles and nerves.

Vialox peptide has been suggested to interfere with nerve and muscle signal transmission. Signals are transmitted in normal conditions after nerves release acetylcholine from their axons. Contraction may occur after acetylcholine transportation through the neuromuscular junction and binds to a receptor on the muscle.

Vialox peptide may halt contraction by binding to the AChR.^[2] Acetylcholine is prevented from binding due to this action, which may induce less binding and fewer muscle contractions.

At the neuromuscular junction, sodium ion release is constrained due to acetylcholine binding to a muscle receptor. Depolarization occurs, which may cause electrical pulses to develop wrinkling and creasing via the muscle contraction. Vialox may inhibit this process by binding to AChR. Vialox peptide inhibits acetylcholine binding when it binds to AChR.

Vialox peptide has been suggested to only affect peripheral AChRs and may not affect central neuronal receptors. Unlike the other nicotinic acetylcholine receptor antagonists. This process suggests that Vialox only acts on the neuromuscular junction. Vialox peptide may potentially reduce skin texture in research cases by up to 11% and relief by 8%, according to one study. Since wrinkle size and ease are considered to be inversely proportional, Vialox may potentially reduce wrinkle development by an average of 8%. Approximately 60% and 47% of the animal subjects were studied.

Vialox (Pentapeptide-3V), composed of lysine, threonine, and serine, is considered to stimulate collagen production while tightening the skin by acting directly on the dermis. Vialox may potentially boost melanin production, a considered protectant against UV damage.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Zhmak, M. N., Utkin, Y. N., Andreeva, T. V., Kudryavtsev, D. S., Kryukova, E. V., Tsetlin, V. I., … & Shelukhina, I. V. E. (2017). U.S. Patent No. 9,550,808. Washington, DC: U.S. Patent and Trademark Office.
2. Reddy, B. Y., Jow, T., & Hantash, B. M. (2012). Bioactive oligopeptides in dermatology: Part II. Experimental dermatology, 21(8), 569-575. https://onlinelibrary.wiley.com/doi/10.1111/j.1600-0625.2012.01527.x

Syn-coll peptide or Palmitoyl Tripeptide-5 is a peptide that has been hypothesized to increase the production of Type I and Type III collagen while inhibiting its degradation (1). It is also known as Palmitoyl Tripeptide-5 or Tripeptide-5. Syn-coll peptide appears to induce these functions by activating the transforming growth factor.

Research has suggested that Syn-coll may function similarly to Thrombospondin-1 by stimulating the breakdown of collagen caused by transforming growth factors. A naturally occurring peptide called TSP-1 is considered to promote TGF- activity. Syn-coll peptide is suggested to host the same properties as TSP-1 in increasing Type I and III collagen levels in dermal (skin) fibroblasts. According to experimental results, Syn-coll may raise type I and III collagen levels by 2-3 folds above normal levels(2). Varga et al. further suggest, ‘Our results indicate that TGF beta causes a marked enhancement of the production of types I and III collagens and fibronectin by cultured normal … dermal fibroblasts. The rate of collagen production by fibroblasts exposed to TGF beta was 2-3-fold greater than that of control cells. These effects were associated with a 2-3-fold increase in the steady-state amounts of types I and III collagen mRNAs and a 5-8-fold increase in the amounts of fibronectin mRNAs as determined by dot-blot hybridization with specific cloned cDNA probes. In addition, the increased production of collagen and fibronectin and the increased amounts of their corresponding mRNAs remained elevated for at least 72 h after the removal of TGF beta. These findings suggest that TGF beta may play a major role in the normal regulation of extracellular matrix production in vivo and may contribute to the development of pathological states of fibrosis’ (2) TSP-1 is a protein found in the extracellular matrix (ECM), and it is considered to be found alongside collagen and elastin.

Research regarding Palmitoyl Tripeptide-5, like TSP-1, suggests that this peptide may improve wound healing (3). It appears to participate in the development of skin structures. The Syn-coll peptide may inhibits matrix metalloproteinase I and III activity (MMP1 and MMP3). Enzymes that degrade collagen are known as matrix metalloproteinases. These enzymes may be beneficial because they recycle collagen, but appear uncontrollably increased to abnormal levels in conditions such as inflammation. As a result, premature skin damage, lines, and creasing along the skin structure may appear (3).

Syn-coll may potentially support the elimination of toxins and reduce the development and depth of wrinkles on the skin surface. Syn-coll appears to interact with the skin, keeping toxins at bay. This procedure may shield from free radicals.

By possibly inhibiting MMP1 and MMP3 activity, Syn-coll peptide may potentially help to prevent collagen breakdown. These hypotheses suggest that Syn-coll peptide may promote the formation of Type I and Type III collagen while inhibiting collagen breakdown by the enzymes, as mentioned earlier.

Syn-coll, a synthetic peptide component, has been hypothesized to have two primary effects. It appears to increase collagen production by replicating the activation of latent transforming growth factor beta, TGF (Tissue Growth Factor), considered a critical component in collagen synthesis. It appears to protect collagen from breakdown by inhibiting matrix metalloproteinases (MMP). Both activities may work together to keep the skin’s structural integrity intact. Compared to a placebo, Syn-coll peptide may be up to 3.5 times more impactful in wrinkle depth reduction. According to the researchers, Palmitoyl Tripeptide-5 may be 60% more effective than Palmitoyl Pentapeptide (5).

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Errante F, Ledwoń P, Latajka R, Rovero P, Papini AM. Cosmeceutical Peptides in the Framework of Sustainable Wellness Economy. Front Chem. 2020 Oct 30;8:572923. doi: 10.3389/fchem.2020.572923.
2. Varga J, Rosenbloom J, Jimenez SA. Transforming growth factor beta (TGF beta) causes a persistent increase in steady-state amounts of type I and type III collagen and fibronectin mRNAs in normal human dermal fibroblasts. Biochem J. 1987 Nov 1;247(3):597-604
3. Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, Almeida IF. Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Pharmaceuticals (Basel). 2021 Jul 21;14(8):702. doi: 10.3390/ph14080702.
4. Fadilah NIM, Rahman MBA, Yusof LM, Mustapha NM, Ahmad H. The Therapeutic Effect and In Vivo Assessment of Palmitoyl-GDPH on the Wound Healing Process. Pharmaceutics. 2021 Feb 1;13(2):193. doi: 10.3390/pharmaceutics13020193.
5. Bucay VW, Day D. Adjunctive skin care of the brow and periorbital region. Clin Plast Surg. 2013 Jan;40(1):225-36. doi: 10.1016/j.cps.2012.09.003
6. Resende DISP, Ferreira MS, Sousa-Lobo JM, Sousa E, Almeida IF. Usage of Synthetic Peptides in Cosmetics for Sensitive Skin. Pharmaceuticals (Basel). 2021 Jul 21;14(8):702. doi: 10.3390/ph14080702

Pal-GHK, also known as Palmitoyl Tripeptide-1 or Palmitoyl Oligopeptide, may act to mitigate the development of creasing in the epidermis and may regulate trans-epidermal water loss.^[1,2] Pal-GHK is a peptide with a fatty acid end and a peptide end. Pal-GHK peptide is a fibroblast stimulant and a minor component of the elastin protein.

 

Potential Function of Pal-GHK Peptide

Palmitoyl Tripeptide-1 may induce the production of fibroblasts at a rapid rate to replenish and regenerate any lost elastin. The GHK-end is connected to the Pal-end, the fatty acid (Palmitoyl) end of Pal-GHK acts as an intermediary. This transport complex appears to improve skin cell penetration.

Pal-GHK peptide appears to activate genes that may change and reset cells. This may be accomplished by attaching Palmitoyl to the peptide sequence, GHK, which may make it more effective for DNA repair genes and increases the expression of the 14 genes that modulate antioxidant production. Following the genetic changes, the action of cell aging may be reduced, as are radicals and toxic agents that cause the development of certain diseases.

Pal-GHK is a modified form of the extracellular matrix-derived peptide GHK that may potentially permeate the stratum corneum and attain the epidermal and dermal skin layers.

Pal-GHK (0.5 M) may increaase collagen synthesis in skin fibroblasts. It may reduce collagen degradation in skin samples exposed to UVA light when examined at a concentration of 6 ppm.

Scientists suggest that combined with the zwitterionic surfactant C12 dodecyl dimethylamine oxide they may investigate the composite’s identity into aggregates, ribbons, and nanobelts. Pal-GHK peptide as an internal standard helped quantify pal-KTTKS in anti-wrinkle creams using LC-MS/MS.

Scientists believe Pal-GHK peptide may activate age-related DNA repair and certain genes. According to new research, the peptide may potentially influence follicle regeneration.

 

Pal-GHK Peptide and Wrinkles

Pal-GHK may protect the extracellular matrix from certain cell aging consequences, according to scientific data^[4]. Shagen et al report that “In a study … leading to statistically significant reductions in wrinkle length, depth and skin roughness. Another study applied both vehicle and palmitoyl tripeptide-1 to the skin … documenting a small but statistically significant increase in skin thickness (~4%, compared to the vehicle alone)The peptide accomplishes this by increasing the production of elastin and collagen.”

Palmitoyl Tripeptide-1 may replenish the skin’s extracellular matrix, reducing wrinkles, smoother skin, and less uneven skin. At the same time, it may protect collagen from degradation caused by Ultraviolet A (UVA) rays. Pal-GHK peptide may be examined solely or combinatorally with Palmitoyl tetrapeptide – Z.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Ferreira, M. S., Magalhães, M. C., Sousa-Lobo, J. M., & Almeida, I. F. (2020). Trending anti-aging peptides. Cosmetics, 7(4), 91.
2. Gorouhi, F., & Maibach, H. I. (2009). Role of peptides in preventing or treating aged skin. International journal of cosmetic science, 31(5), 327-345.
3. Park, S. I., An, G. M., Kim, M. G., Heo, S. H., & Shin, M. S. (2020). Enhancement of Skin Permeation of Anti-wrinkle Peptide GHKs Using Cell Penetrating Peptides. Korean Chemical Engineering Research, 58(1), 29-35. https://doi.org/10.9713/KCER.2020.58.1.29

TB-500 peptide is a synthetic version of Thymosin Beta-4 found in animal cells.^[1] TB-500 is a peptide sequence composed of 43 amino acid molecules and a member of 16 cohabiting molecules with high sequence conservation and localization in tissues and circulating cells. In eukaryotic cells, the TB-500 peptide is suggested to bind to actin, inhibit actin polymerization, and may be an actin-cloistering molecule.

According to studies, TB-500 may be upregulated four to sixfold after early blood vessel formation^[2]. It appears to promote the formation of new blood vessels from existing ones. The peptide may stimulate wound healing. It appears to upregulate the rejuvenating time of muscle fibers and their cells. TB-500 peptide may also promote cell migration by interacting with actin in the cell cytoskeleton. The central small amino acid long-actin binding domain is considered to be responsible for wound healing and blood cell reproduction. These characteristics may be activated by increasing endothelial cell migration and keratinocytes, possibly increasing the synthesis of Extra matrix-degrading enzymes.

According to scientific data, TB-500 is a synthetic peptide with wound healing and anti-inflammatory potential.^[2] This peptide differs from others in that it appears to promote keratinocyte and endothelial migration. It has a low molecular weight and does not appear to bind to the extracellular matrix, implying that it may potentially travel long distances through tissues. The most important mechanism of action of the TB-500 peptide is its potential to modulate actin activity.

 

TB-500 Peptide Research

TB-500 peptide may be concentrated at injury sites, where it may improve wound healing and repair in the brain, spinal cord, skin, heart, bones, and organs.^[4]

When released from platelets, TB-500 peptide may play a potential cellular role in immune regulation and inflammation. As a result, TB-500 peptide may increase B cells, which regulate antibody activation. It may increase Actin levels to promote tissue repair after injury and potentially stimulate T cell synthesis to improve immune system function.^[5]

TB-500 and Blood Clots: TB-500 peptide may be a vital ancillary in mitigating blood clots and might regulate the formation of blood vessels.

TB-500 and Soft Tissue Damage: The potential of TB-500 peptide to promote angiogenesis and reduce inflammation may result in muscle, ligament, and tendon recovery.

TB-500 and Muscular Function: TB-500 peptide may potentially increase the rate of muscle repair and growth rate, including regulating muscle spasms.

TB-500 and Neurological and Cardiovascular Damage: TB-500 peptide may potentially promote angiogenesis, including neuron formation and better brain axonal density.

TB-500 and Matrix Metalloproteinase Expression in Tissue Repair: Wound healing impairment is common in diabetic cases of immobility. According to research, TB-500 peptide may potentially improve dermal wound repair in rats, dB/dB diabetic mice, and aged mice.^[6] Philip et al. concluded “that thymosin β4 is active for wound repair in models of impaired healing and may have efficacy in chronic wounds.” In normal rats and mice, the peptide appears to potentially promote corneal repair. TB-500 may regulate matrix metalloproteinase (MMP) expression in wound repair cells. RT-PCR analysis of whole excised mouse dermal wounds on days 1, 2, and 3 after injury suggested that TB-500 peptide increased the expression of several metalloproteinases, including MMP-2 and -9, by several folds on days two after wounding. The metalloproteinases secreted by activated monocytes in response to exogenous TB-500 in the wound were also studied. They suggested that the peptide increased MMP-1 and MMP-9 levels.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Ho, E. N., Kwok, W. H., Lau, M. Y., Wong, A. S., Wan, T. S., Lam, K. K., Schiff, P. J., & Stewart, B. D. (2012). Doping control analysis of TB-500 peptide, a synthetic version of an active region of thymosin β₄, in equine urine and plasma by liquid chromatography-mass spectrometry. Journal of chromatography. A, 1265, 57–69. https://doi.org/10.1016/j.chroma.2012.09.043
2. Grant, D. S., Rose, W., Yaen, C., Goldstein, A., Martinez, J., & Kleinman, H. (1999). Thymosin beta4 enhances endothelial cell differentiation and angiogenesis. Angiogenesis, 3(2), 125–135. https://doi.org/10.1023/a:1009041911493
3. Malinda, K. M., Sidhu, G. S., Mani, H., Banaudha, K., Maheshwari, R. K., Goldstein, A. L., & Kleinman, H. K. (1999). Thymosin beta4 accelerates wound healing. The Journal of investigative dermatology, 113(3), 364–368. https://doi.org/10.1046/j.1523-1747.1999.00708.x
4. Goldstein, A. L., Hannappel, E., & Kleinman, H. K. (2005). Thymosin β4: actin-sequestering protein moonlights to repair injured tissues. Trends in molecular medicine, 11(9), 421-429.
5. Huff, T., Otto, A. M., Müller, C. S., Meier, M., & Hannappel, E. (2002). Thymosin β4 is released from human blood platelets and attached by factor XIIIa (transglutaminase) to fibrin and collagen. The FASEB journal, 16(7), 691-696.
6. Philp, D., Badamchian, M., Scheremeta, B., Nguyen, M., Goldstein, A. L., & Kleinman, H. K. (2003). Thymosin β4 and a synthetic peptide containing its actin‐binding domain promote dermal wound repair in db/db diabetic mice and in aged mice. Wound repair and regeneration, 11(1), 19-24.

PTD-DBM peptide has been suggested to promote Wnt/Beta-catenin signaling by inhibiting CXXC5 binding to Disheveled (Dvl), an upstream component of the Wnt/-catenin pathway. Protein Transduction Domain-fused Disheveled Binding Motif (PTD-DBM) is a synthetic peptide that appears to work in conjunction with CXXC5. This hair loss-linked endogenous protein may act as a negative feedback modulator of the Wnt/-catenin pathway.

PTD-DBM Peptide Overview

CXXC5 appears to act as a reversible modulator on the Wnt/-catenin nerve tract, which is involved in wound healing and hair regrowth. It is known as “the hair loss catalytic enzyme”. CXXC5 forms a bond with the Dvl protein, which may inhibit hair regeneration and follicle development. PTD-DBM has been hypothesized to prevent CXXC5 from binding to the disheveled protein. It may act as a negative modulator of the entire process.^[1] If PTD-DBM prevents CXXC5 from becoming a disheveled protein, the Wnt/-catenin pathway may be activated, inducing hair follicle regrowth and wound-induced hair follicle neogenesis. PTD-DBM is suggested to inhibit the activities of enzymes and hormones that shrink follicles, gradually restoring the strands at the stem cell level. PTD-DBM peptide may prevent follicle volume loss while stimulating the formation of new cavities for follicle growth.

 

PTD-DBM and Androgenetic Alopecia

Androgenetic Alopecia is characterized by the regression of follicle loss in the vertex. It may progress and induce total follicle loss. The anagen, catagen, and telogen phase are the three stages of follicle growth. The anagen phase may be shortened due to androgen hypersecretion, specifically testosterone. It may induce follicle growth to thin and shed, and the anagen phase may last only a few months.

The most crucial cellular pathway that is considered to regulate follicle growth is the Wnt/-catenin pathway. Wnt proteins are released, which may bind to the LDL-related protein LRP, deactivating glycogen synthase kinase-3 (GSK-3). GSK-3 appears to inhibit -catenin’s actions in the hair follicle.

According to Professor Kang-Yell Choi’s research, CXXC-type zinc finger protein 5 (CXXC5) may be expressed aggressively in cases of Alopecia.^[3] CXXC5 appear to inhibit the Wnt/-catenin signaling pathway. CXXC5 may accomplish this by binding to the Dvl protein, hindering the growth and development of both new and existing follicles.

By inhibiting the actions of CXXC5 and Dvl protein, PTD-DBM may potentially reduce the prevalence of androgenetic alopecia, resulting in increased follicle growth and the anagen phase of the growth cycle. PTD-DBM potential actions may result in positive impact; when the peptide is in symbiosis with valproic acid, its potency has been suggested to increase.

 

PTD-DBM and Tissue Repair

The Wnt/-catenin signaling pathway is considered to be essential for wound healing and skin break fibrosis. The CXXC5 may regulate it via a negative feedback mechanism. The CXXC5 appears to bind to the Disheveled (Dvl) protein, inhibiting the Wnt/-catenin signaling pathway. Inhibiting CXXC5 activities in mice appears to promote wound healing by stimulating collagen and keratin synthesis, specifically skin wound healing.^[2] Furthermore, PTD-DBM has been suggested to inhibit the CXXC5-Dvl domain’s actions by preventing protein-to-protein interactions between CXXC5 and Dvl proteins. As a result, the Wnt/-catenin pathway may become more active, inducing collagen and keratin synthesis and increased dermal fibrosis.

 

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing.  Bodily introduction of any sort is strictly prohibited by law.  All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

 

References

---

1. Lee, S. H., Seo, S. H., Lee, D. H., Pi, L. Q., Lee, W. S., & Choi, K. Y. (2017). Targeting of CXXC5 by a Competing Peptide Stimulates Hair Regrowth and Wound-Induced Hair Neogenesis. The Journal of investigative dermatology, 137(11), 2260–2269. https://doi.org/10.1016/j.jid.2017.04.038
2. Lee SH, Kim MY, Kim HY, Lee YM, Kim H, Nam KA, Roh MR, Min do S, Chung KY, Choi KY. The Dishevelled-binding protein CXXC5 negatively regulates cutaneous wound healing. J Exp Med. 2015 Jun 29;212(7):1061-80. doi: 10.1084/jem.20141601. Epub 2015 Jun 8. PMID: 26056233; PMCID: PMC4493411.
3. Ryu YC, Lee DH, Shim J, Park J, Kim YR, Choi S, Bak SS, Sung YK, Lee SH, Choi KY. KY19382, a novel activator of Wnt/β-catenin signalling, promotes hair regrowth and hair follicle neogenesis. Br J Pharmacol. 2021 Jun;178(12):2533-2546. doi: 10.1111/bph.15438. Epub 2021 May 5. PMID: 33751552; PMCID: PMC8251890.
4. Rahman M, Nguyen H. Valproic Acid. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559112/