N-Acetyl DBP-MAF Amidate - 1mg, 10mg

STRUCTURE

Sequence:  Ac- Thr-Pro-Thr-Glu-Leu-Ala-Lys-Leu-Val-Asn-Lys-Arg-Ser-Glu-NH2

Molecular formula: C25H37N5O6

Molecular weight :  503.60 g/mol

Peptide Purity: Greater than 98%

Other details: No TFA Salt

Storage: Lyophilized peptide must be stored at -20°C and peptide solution at +4°C

DESCRIPTION

Gc-MAF Frag or DBP-MAF (Vitamin D-Binding Protein Macrophage Activating Factor or Gc Protein-Derived Macrophage Activating Factor) is a critical fragment derived from the Vitamin D-Binding Protein (DBP), a multifunctional plasma protein responsible for a variety of roles, such as transporting vitamin D metabolites and modulating immune responses. The DBP-MAF fragment represents a specific part of DBP that has been enzymatically altered to become a macrophage-activating factor. This fragment has garnered significant interest in the scientific and medical communities due to its potential therapeutic applications in enhancing immune system function, particularly in treating cancer, chronic infections, and autoimmune diseases.

DBP-MAF is produced when the Vitamin D-Binding Protein undergoes specific enzymatic changes, such as the removal of sialic acid and galactose residues, leaving behind N-acetylgalactosamine (GalNAc). This specific modification allows the protein to activate macrophages by interacting with lectin receptors on their surface.

The fragment’s ability to bind to macrophages and initiate an immune response makes it a promising candidate for therapies that rely on immune modulation. The DBP-MAF fragment is recognized for its ability to activate macrophages and boost the immune system by encouraging these immune cells to phagocytose pathogens and tumor cells.

The DBP-MAF fragment works by activating macrophages, which are key cells in the immune system responsible for detecting and eliminating harmful pathogens and abnormal cells, including cancerous ones. The process of activation involves several key steps:

1. Enzymatic Conversion: The DBP-MAF fragment is generated when the Vitamin D-Binding Protein undergoes enzymatic modifications, typically involving beta-galactosidase and sialidase, which remove sugars from the protein and expose a GalNAc residue at a critical site, often Thr420.
2. Macrophage Activation: Once the DBP-MAF fragment interacts with macrophages via lectin receptors like CLEC10A (also known as the macrophage galactose-type lectin, or MGL), it triggers signaling pathways within the macrophages. This leads to their activation, causing them to release pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6.
3. Enhancement of Phagocytosis: Activated macrophages become more efficient at phagocytosis, meaning they can engulf and destroy harmful pathogens, dead cells, and tumor cells. This immune-stimulating effect is the core mechanism through which DBP-MAF exerts its benefits.
4. Tumor Suppression and Immune Surveillance: The activated macrophages play a vital role in tumor suppression by identifying and destroying cancer cells. Additionally, DBP-MAF's influence on macrophages enhances the body’s overall immune surveillance, reducing the risk of tumor metastasis and aiding in the control of chronic infections.

The potential of DBP-MAF is rooted in its ability to enhance the immune system’s ability to fight various diseases. Some key benefits include:

1. Cancer Treatment:

1. • DBP-MAF has shown promise in cancer therapies due to its macrophage-activating properties, which lead to the destruction of cancer cells. Several preclinical studies have demonstrated that DBP-MAF can reduce tumor growth and metastasis in cancers like breast cancer, prostate cancer, and melanoma.
   • Its role in inhibiting angiogenesis, which is the formation of new blood vessels that feed tumors, is particularly important in cancer treatment. By limiting the blood supply to tumors, DBP-MAF can reduce tumor proliferation and metastasis.
2. Chronic Infections:
   • In cases of chronic infections such as HIV and hepatitis C, DBP-MAF may assist the immune system by activating macrophages to clear infected cells and reduce the viral load. This enhanced immune function is crucial in managing diseases where the immune system is otherwise overwhelmed.
3. Autoimmune Disorders:
   • DBP-MAF’s immune-modulating abilities can also benefit autoimmune diseases by promoting a balanced immune response. In diseases such as rheumatoid arthritis, multiple sclerosis, and lupus, where the immune system mistakenly attacks healthy tissue, DBP-MAF can reduce the severity of immune responses, helping to alleviate symptoms.
4. Autism Spectrum Disorder (ASD):
   • While controversial, there is some emerging research suggesting that immune modulation through DBP-MAF might help improve certain symptoms in children with autism spectrum disorder. The underlying theory is that immune dysfunction may contribute to the symptoms of autism, and by restoring immune balance, DBP-MAF could potentially alleviate some of these issues.
5. General Immune Enhancement:
   • For individuals with compromised immune systems, such as the elderly or those undergoing treatments like chemotherapy, DBP-MAF’s ability to activate macrophages can strengthen the immune system and reduce the risk of infections.

DBP-MAF has been investigated for its role in several diseases, including:

1. Cancer: As mentioned earlier, DBP-MAF has been explored as a potential treatment for a variety of cancers, including breast cancer, prostate cancer, and colorectal cancer. By enhancing macrophage activity, DBP-MAF can suppress tumor growth and prevent the spread of cancer cells. In preclinical and clinical studies, DBP-MAF has demonstrated a reduction in tumor size and metastasis, particularly in solid tumors like melanoma and pancreatic cancer.
2. Chronic Fatigue Syndrome (CFS): There is some evidence to suggest that DBP-MAF could help alleviate the symptoms of Chronic Fatigue Syndrome (CFS) by modulating immune responses. In CFS, immune dysfunction is thought to play a role in the fatigue and other symptoms experienced by patients.
3. Infectious Diseases: DBP-MAF may be beneficial in treating chronic viral infections, particularly those that evade the immune system, such as HIV and hepatitis B or C. By boosting macrophage function, DBP-MAF could improve the body's ability to clear infected cells.
4. Autoimmune Diseases: Diseases like rheumatoid arthritis and multiple sclerosis may benefit from DBP-MAF’s immune-balancing effects. By modulating macrophage activity, DBP-MAF could reduce the inflammation and tissue damage associated with these diseases.

The pharmacodynamics of DBP-MAF involve its interaction with macrophages and its subsequent effects on the immune system:

• Macrophage Activation: DBP-MAF stimulates macrophages by binding to lectin receptors, specifically CLEC10A, on their surface. This binding triggers intracellular signaling pathways that lead to the production of pro-inflammatory cytokines, such as TNF-α and IL-6, which enhance the immune response.
• Cytokine Release: Upon activation, macrophages secrete cytokines that recruit other immune cells to the site of infection or tumor growth, creating a robust immune response.
• Phagocytosis: Activated macrophages increase their ability to engulf and destroy pathogens, cancer cells, and dead tissue. This enhanced phagocytic activity is one of the primary therapeutic mechanisms of DBP-MAF.
• Angiogenesis Inhibition: DBP-MAF also appears to influence angiogenesis by reducing the formation of new blood vessels around tumors. This can starve tumors of nutrients and slow their growth.

The acetylation and amidation of Gc-MAF Frag/DBP-MAF provide the peptide with:

• Greater stability: C-terminal amidation can reduce enzymatic degradation of the peptide, protecting it from the action of carboxypeptidases and increasing its stability in the body.
• Longer half-life: Increased resistance to enzymatic degradation can result in a longer half-life, allowing the peptide to remain active in the system for a longer period of time.
• Higher binding affinity: The modification can influence the peptide’s binding affinity to its target receptors, potentially improving its efficacy.
• Improved pharmacokinetic properties: The modified chemical structure can also enhance pharmacokinetic properties, facilitating more efficient distribution and action in the body

REFERENCES

O. Kisker at al., "Vitamin D binding protein-macrophage activating factor (DBP-maf) inhibits angiogenesis and tumor growth in mice" [PubMed]

K. Gumireddy et al., "Mitogen-activated protein kinase pathway mediates DBP-maf-induced apoptosis in RAW 264.7 macrophages" [PubMed]

K.J. Gregory et al., "Vitamin D binding protein-macrophage activating factor directly inhibits proliferation, migration, and uPAR expression of prostate cancer cells" [PubMed]

S. Pacini et al., "Effects of vitamin D-binding protein-derived macrophage-activating factor on human breast cancer cells" [PubMed]

S. Kalkunte et al., "Inhibition of angiogenesis by vitamin D-binding protein: characterization of anti-endothelial activity of DBP-maf" [PubMed]

K. Nonaka et al., "Vitamin D binding protein-macrophage activating factor inhibits HCC in SCID mice" [PubMed]

E. Saburi et al., "Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside" [PubMed]

D.S. Rehder et al., "Glycosylation status of vitamin D binding protein in cancer patients" [PubMed]

DISCLAIMER

This product is intendend for lab research and development use only. These studies are performed outside of the body. This product is not medicines or drugs and has not been approved by the FDA or EMA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law. This product should only be handled by licensed, qualified professionals.

All product information provided on this website is for informational and educational purposes only.