Description

Peptide T Peptide Vial

CAS Number	106362-32-7
Other Names	Peptide-t, Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr, UNII-05DYM3ZS1X, 05DYM3ZS1X
IUPAC Name	(2S,3R)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxybutanoic acid
Molecular Formula	C₃₅H₅₅N₉O₁₆
Molecular Weight	857.87
Purity	≥99% Pure (LC-MS)
Powder Availability	1 milligram vial, 5 milligrams vial, 10 milligrams vial (lyophilized/freeze-dried)
Storage Condition	Store cold, keep refrigerated. Do NOT freeze.
Terms	All products are for laboratory developmental research USE ONLY. Products are not for human consumption.

**Important Information: Each peptide comes lyophilized/freeze-dried and must be reconstituted with Bacteriostatic Water in order to be dispensable in liquid form.

Watch How To Reconstitute Peptide Video Here

What is Peptide T?

Peptide T (Ala-Ser-Thr-Thr-Thr-Asn-Tyr-Thr) is a synthetic short octapeptide originally discovered by neuroscientist and immunologist Candace pert and Michael Ruff in 1986. The compound is derived from the HIV envelope protein, gp120, which is capable of blocking the binding and infection of different viral strains to the CCR5 receptors. Because of its ability to inhibit the binding of gp120, current research highlights the potential of Peptide T to act as an antiviral agent in the treatment of HIV [1]. Additionally, the peptide is being investigated for its ability to treat various other autoimmune and/or inflammatory conditions such as psoriasis, while the inhibitory effects of Peptide T have also been applied to the levels of CXCR4 and CCR5 chemokine receptors.

Short peptides play a crucial role in various different biological processes. Short peptide chains like Peptide T are far more cost-effective, easily modified, absorbed, and more accessible than their long chain counterparts. It is important to be able to structurally modify peptides as this can lead to enhanced physicochemical properties, as well as increased stability of the compound. The peptides can be further stabilized in their bioactive conformation by making modifications to the backbone, sequence length, side chains, C-terminus, and N-terminus. Making these changes may also result in reduced renal clearance, increased membrane permeability and target selectivity, and overall increased efficiency of the peptide.

Additionally, efficiency and bioavailability of a peptide is influenced by conjugating cell-penetrating peptides, allowing the compound to cross the cellular membrane and access intracellular targets. Research is being conducted in order to investigate how peptide delivery and cellular uptake is enhanced by the conjugation of non-peptide motifs to short peptide chains. The pharmacokinetic profile of peptides can be improved through the use of peptoids. While peptoids are based on native peptides, other methods, such as phage display, can also be used to assist in the development of short peptides, allowing the chains to better survive proteolytic degradation in the GI tract. These peptides are also able to be used as therapeutic agents that antagonize the interleukin-23 receptors and combat the build up of Factor XIa in cases of chronic GI distress related to Crohn’s disease and ulcerative colitis [2].

Research surrounding the use of ultra-short peptides has revealed that “less is more” [2]. This indicates that ultra-short peptides have many benefits including easier and cheaper economic synthesis, a higher degree of stability, and enhanced tissue penetration. When compared to long peptide chains, short peptides have better biocompatibility and biodegradability, as well as the ability to promote growth and proliferation of diverse cells. Ultra-short peptides are also compatible with oral delivery which improves both the safety and efficacy of the drug. These compounds are also capable of addressing problems related to a low half-life as they can be utilized in a “controllable release” format [2]. As it was previously mentioned, short peptides can potentially be used to treat disorders of the GI tract, however, it has many bioapplications and has shown promise in repairing brain tissues and treating neurodegenerative diseases, as well as inhibiting the growth of cancer cells.

Short peptides also play a critical role throughout the immune system. Current research is being conducted in order to determine how they may be incorporated into vaccines; so far, peptide-based vaccines have been shown to have many advantages over typical vaccines. They have the ability to elicit engineered epitope-specific immune responses, they do not cause severe allergic or inflammatory responses, they provide direct immune responses, the products can be developed with high precision and reproducibility, and they are more stable than whole proteins. While there are no peptide-based vaccines currently on the market, many of them are currently under development with the goal of targeting several infectious diseases such as COVID-19, AIDS, and malaria [2].

Altered peptide ligands (APL) have been more frequently used in the treatment of inflammatory autoimmune diseases such as myasthenia gravis, type-1 diabetes, and multiple sclerosis (MS). APLs are typically produced when the T cell receptor (TCR) contact sites are manipulated in immunogenic peptides. In cases of myasthenia gravis, the disease is regulated by CD4+ T-cells that recognize various peptide epitopes. Research has found that by mutating a single amino acid on the epitopes of the acetylcholine receptor alpha-subunit, the autoimmune response was successfully inhibited. Type-1 diabetes is regulated by CD4+ and CD8+ T cells, however, by mutating two TCR contact amino acids, an influx of anti-inflammatory compounds IL-4, IL-5, and IL-10 were released. Similar mechanisms were used in the experimental treatment of MS, however, different peptide epitopes were recognized in cases of this autoimmune disease [2].

Main Research Findings

1) The research team of Raychaudhuri et. al found that the peptide T analogue, DAPTA, may have anti-chemotaxic properties that explain the compound’s ability to treat psoriasis.

2) Treatment with peptide T was found to increase both the distribution and density of Langerhans’ cells in the epidermis to normal levels in individuals experiencing symptoms of psoriasis.

3) Research shows that peptide T has the potential to block the binding of gp120 to brain tissue, however, more conclusive data should be gathered in order to accurately determine the ability of the peptide to treat cognitive decline related to HIV.

Selected Data

1) The analogous to synthetic Peptide T, d-Ala-Peptide T amide (DAPTA), was shown to inhibit the binding of the HIV infection to human T cells in vitro, as well as inhibit the binding of HIV envelope to brain membranes. While conducting further research on the potential of Peptide T to treat HIV, it was discovered that psoriasis was improved as a side effect of treatment. However, the research team that conducted the initial study was not able to identify the mechanism through which Peptide T treats the autoimmune disorder. Current hypotheses suggest that Peptide T may be capable of blocking CD4 receptors and preventing the penetration of the retrovirus causing psoriatic symptoms, or that the peptide directly affects the functioning of the CD4+ cells throughout the psoriatic lesions. The psoriatic lesions also house an increased number of a beta-chemokine, RANTES. It is also important to note that lymphomononuclear cells are crucial to the inflammatory process as the play a role in not only initiating but maintaining the process through cascade mechanisms that include inflammatory cytokines and chemokines such as IL-2 and RANTES, respectively [3].

The study conducted by the research team of Raychaudhuri et. al included 15 patients experiencing moderate to severe symptoms of psoriasis. There were 14 male and 1 female test subjects of the average age of 39 years old. Five individuals without psoriasis were also included in the study to act as a control group. There were 4 male and 1 female test subjects of the average age of 37 years old. Heparinized blood samples were collected from each test subject and subjected to gradient centrifugation in order to isolate peripheral blood mononuclear cells (PBMC). PBMCs were then washed three times with a balanced salt solution, followed by resuspension in a complete medium composed of RPMI-1640, 1% penicillin, 2mM glutamine, streptomycin, and 10% fetal calf serum [3]. The purity of monocytes and lymphocytes found in the sample was assessed by alpha-naphthyl acetate esterase staining and indirect fluorescent antibody staining, respectively.

2) Psoriasis is typically associated with dysfunction of the Langerhans cells related to their ability to migrate from the epidermis of the skin. In their role as dendritic cells, Langerhans cells play an important role in the immune system. Typically these cells activate in response to a specific stimulus, however, in individuals with psoriasis, this response was almost completely absent [4]. The research team of Wang et. al examined dendritic cells marked by protein S-100 throughout the suprabasal epidermal layers [5].

These dendritic cells were found to be Langerhans’ cells that were further investigated for their response to treatment with peptide T in psoriatic lesioned skin. There were nine patients experiencing symptoms of psoriasis that were administered treatment with peptide T. Over a 28 day experimental treatment period each test subject received a daily, 2 mg dose of the peptide mixed in with 500 ml of saline. Every week throughout the treatment sections of the involved skin were analyzed using S-100 antiserum with indirect immunofluorescence [5].

3) Neuropsychiatric illnesses such as mood and anxiety disorders are very common in patients with HIV and AIDS. In addition to neuropsychiatric illnesses, cognitive impairment, typically in the form of dementia, is linked to HIV infection. The research team of Heseltine et. al examined whether peptide T could be considered an effective treatment for cognitive impairments related to HIV, considering that the peptide has shown to protect neurons and brain tissue by inhibiting the binding of gp120.

Peptide T was administered to test subjects intranasally in 2 mg doses 3 times a day for 6 months. Several variables, including CD4+ count, antiretroviral therapy, and the severity of impairment, were taken into account when randomizing participants into study groups. Inclusion in the study was based on whether an individual was HIV-seropositive with neuropsychological (NP) screening test scores indicating the presence of cognitive deficits. The NP screening test yielded 23 scores from each participant that were then standardized to develop a global score [6].

The test was administered prior to experiment and at the end of the study. The primary efficacy endpoint the research team was comparing was the change in global NP scores after 6 months of experimental treatment with peptide T. Secondary measures assessed by the research team were 7 cognitive domain and deficit scores. These scores were related to both global and domain performance of the participants on the NP screening test. In addition to the initial 6 months of treatment, any test subject that completed both the baseline and study endpoint NP screening were included in further efficacy analyses that were meant to examine both baseline NP deficits and C4+ cell counts [6].

Discussion

1) The results of the study conducted by Raychaudhuri et. al reported upon the inhibitory effects of DAPTA on RANTES and fmlp-induced chemotaxis of monocytes and lymphocytes. Overall, the data found that the inhibitory effects of DAPTA peaked at 10^-9, confirmed through analysis of variance testing. However, the antichemotactic qualities of DAPTA remain unclear, however, it has been suggested that it may be receptor-mediated considering that Peptide T has been shown to competitively bind with RANTES and fmlp receptors [3].

Figure 1: Effects of DAPTA on RANTES-mediated (A) monocytes and (B) lymphocytes chemotaxis.

2) Results of the study conducted by Wang et. al reported that prior to treatment with peptide T and in comparison to the healthy cells of the control group, there were significantly reduced numbers of Langerhans cells throughout the epidermal layer of skin affected by psoriasis plaques. It is important to mention that in some cases the Langerhans cells in the epidermis of individuals with psoriasis were completely gone. While the amount of Langerhans cells in the dermis was significantly diminished, the number of dendritic cells in the dermal layer of skin increases and tends to gather in clusters around different vascular structures [5].

Psoriasis is thought to be caused by the loss of Langerhans cells from activation in the immune system and migration from the epidermis to lymph vessels. However, following treatment with peptide T, four out of the nine patients included in the study experienced significant histopathological improvements in their psoriasis. Any improvements were characterized as a reduction in dendritic cells in the dermal layer of skin, and an increase in the Langerhans cells in the epidermal layer of skin. The increase in Langerhans cells and their corresponding changes in distribution and density indicate the occurrence of cellular rearrangement during and/or after the course of treatment with peptide T [5].

3) The results of the study conducted by Heseltine et. al did not find a statistically significant difference in global NP screening test scores, deficit scores, or individual domains, when comparing the experimental group treated with peptide T and the control group. However, pilot studies found that administration of peptide T to HIV-seropositive patients with impaired cognitive functioning found that the peptide was linked to improved cognition. That being said, further research should be conducted in order to thoroughly investigate the relationship between peptide T administration and cognitive impairments [6].

While comparison of the NP screening test scores resulted in inconclusive data, the additional analyses conducted examining changes in NP deficits and CD4+ cell counts revealed that these measures saw greater improvement in the experimental groups treated with peptide T. Improvements specifically occurred in patients that had a CD4+ cell count above 200 cells/µL at the beginning of the study. Similarly, improvements in NP global deficit scores following treatment with peptide T were more pronounced in patients with baseline scores of at least 0.5. Additionally, it was mentioned that general cognitive deterioration was found to be more common amongst the participants in the control group [6].

Disclaimer

**LAB USE ONLY**
*This information is for educational purposes only and does not constitute medical advice. THE PRODUCTS DESCRIBED HEREIN ARE FOR RESEARCH USE ONLY. All clinical research must be conducted with oversight from the appropriate Institutional Review Board (IRB). All preclinical research must be conducted with oversight from the appropriate Institutional Animal Care and Use Committee (IACUC) following the guidelines of the Animal Welfare Act (AWA).

Citations

[1] Sáez-Torres I, Espejo C, Pérez JJ, Acarín N, Montalban X, Martínez-Cáceres EM. Peptide T does not ameliorate experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Clin Exp Immunol. 2000 Jul;121(1):151-6. doi: 10.1046/j.1365-2249.2000.01259.x. PMID: 10886253; PMCID: PMC1905669.

[2] Apostolopoulos V, Bojarska J, Chai TT, Elnagdy S, Kaczmarek K, Matsoukas J, New R, Parang K, Lopez OP, Parhiz H, Perera CO, Pickholz M, Remko M, Saviano M, Skwarczynski M, Tang Y, Wolf WM, Yoshiya T, Zabrocki J, Zielenkiewicz P, AlKhazindar M, Barriga V, Kelaidonis K, Sarasia EM, Toth I. A Global Review on Short Peptides: Frontiers and Perspectives. Molecules. 2021 Jan 15;26(2):430. doi: 10.3390/molecules26020430. PMID: 33467522; PMCID: PMC7830668.

[3] Raychaudhuri SK, Raychaudhuri SP, Farber EM. Anti-chemotactic activities of peptide-T: a possible mechanism of actions for its therapeutic effects on psoriasis. Int J Immunopharmacol. 1998 Nov;20(11):661-7. doi: 10.1016/s0192-0561(98)00020-4. PMID: 9848397.

[4] Cumberbatch M, Singh M, Dearman RJ, Young HS, Kimber I, Griffiths CE. Impaired Langerhans cell migration in psoriasis. J Exp Med. 2006 Apr 17;203(4):953-60. doi: 10.1084/jem.20052367. Epub 2006 Mar 27. PMID: 16567387; PMCID: PMC2118293.

[5] Wang L, Hilliges M, Talme T, Marcusson JA, Wetterberg L, Johansson O. Rearrangement of S-100 immunoreactive Langerhans’ cells in human psoriatic skin treated with peptide T. J Dermatol Sci. 1995 Jan;9(1):20-6. doi: 10.1016/0923-1811(94)00346-g. PMID: 7727353.

[6] Heseltine PN, Goodkin K, Atkinson JH, Vitiello B, Rochon J, Heaton RK, Eaton EM, Wilkie FL, Sobel E, Brown SJ, Feaster D, Schneider L, Goldschmidts WL, Stover ES. Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment. Arch Neurol. 1998 Jan;55(1):41-51. doi: 10.1001/archneur.55.1.41. PMID: 9443710.

PEPTIDES PREFER THE COLD
Keep peptide vials refrigerated at all times to reduce peptide bond breakdown. DO NOT FREEZE. Most peptides, especially shorter ones, can be preserved for weeks if careful.
Always swab the top of the vial with an alcohol wipe, rubbing alcohol or 95% ethanol before use.
Before drawing solution from any dissolved peptide vial, fill the pin with air to the same measurement you will be filling with solution, ie. if you plan to take 0.1 ml, first fill the pin with 0.1ml of air, push the air into the vial, and then draw the peptide back up to the 0.1 ml marker. Doing so will maintain even pressure in the vial. Always remember to remove air bubbles from the pin by flicking it gently, pin side up, and pushing bubbles out. In addition, push out a tiny amount of solution to ensure there is no air left in the metal tip.

ONLY MIX WITH STERILE BACTERIOSTATIC WATER
The purity and sterility of bacteriostatic water are essential to prevent contamination and to preserve the shelf-life of dissolved peptides.
Push the pin through the rubber stopper at a slight angle, so that you inject the bacteriostatic water toward the inside wall of the vial, not directly onto the powder.
Lyophilized peptide should be stored at -20°C (freezer), and the reconstituted peptide solution at 4°C (refrigerated). Do not freeze once reconstituted.
NEVER SHAKE A VIAL TO MIX.

Air bubbles are unfavorable to the stability of proteins.

Peptide T is sold for laboratory research use only. Terms of sale apply. Not for human consumption, nor medical, veterinary, or household uses. Please familiarize yourself with our Terms & Conditions prior to ordering.