CJC-1295: With and Without DAC - Research Comparison

CJC-1295: With and Without DAC - Research Comparison

CJC-1295 is a synthetic peptide analog of growth hormone-releasing hormone (GHRH), also known as growth hormone-releasing factor (GRF). It is used in research settings to stimulate the release of endogenous growth hormone (GH) from the pituitary gland. Two main forms of CJC-1295 are available: CJC-1295 without Drug Affinity Complex (DAC), often referred to as Mod GRF 1-29, and CJC-1295 with DAC. The key difference lies in their pharmacokinetic profiles and duration of action.

Molecular Structure and Mechanism of Action

Both CJC-1295 variants exert their effects by binding to the GHRH receptor on pituitary somatotrophs, triggering the release of GH. However, the presence of DAC profoundly alters the peptide's half-life.

CJC-1295 Without DAC (Mod GRF 1-29)

Mod GRF 1-29 is a modified version of the original GHRH(1-29) sequence. Specifically, the amino acid substitutions are at positions 2 (alanine replaced by D-alanine), 8 (glutamine replaced by alanine), 15 (isoleucine replaced by leucine), and 27 (alanine replaced by glycine). These modifications enhance its stability and resistance to degradation by enzymes like dipeptidyl peptidase IV (DPP-IV), resulting in a longer half-life compared to native GHRH. Despite these improvements, Mod GRF 1-29 still has a relatively short half-life of approximately 30 minutes.

CJC-1295 With DAC

CJC-1295 with DAC consists of Mod GRF 1-29 conjugated to a Drug Affinity Complex (DAC). The DAC is typically a maleimide-activated polyethylene glycol (PEG) moiety. The maleimide group reacts with a cysteine residue on the peptide (usually added for this purpose). This conjugation increases the peptide's molecular weight and significantly extends its half-life. The DAC binds to serum albumin, providing protection from enzymatic degradation and renal clearance. This prolonged half-life allows for less frequent administration, potentially improving convenience in research protocols. The half-life of CJC-1295 with DAC can be several days, often reported between 6-8 days in human studies.

Research Applications

Both CJC-1295 variants are primarily used in research settings to study the effects of elevated GH levels on various physiological processes. These include:

• Muscle Growth and Repair: Investigating the anabolic effects of GH on skeletal muscle.
• Fat Metabolism: Studying the lipolytic effects of GH and its influence on body composition.
• Bone Density: Exploring the role of GH in bone remodeling and maintenance.
• Cognitive Function: Examining the potential neuroprotective effects of GH and its impact on cognitive performance.
• Aging and Longevity: Investigating the role of GH in age-related decline and potential interventions to promote healthy aging.

The choice between CJC-1295 with and without DAC depends on the specific research question and the desired pharmacokinetic profile. Mod GRF 1-29 allows for more pulsatile GH release, mimicking the natural secretion pattern. CJC-1295 with DAC, on the other hand, provides a more sustained and prolonged elevation of GH levels.

Quality Markers to Look For

Ensuring the quality of CJC-1295 peptides is crucial for obtaining reliable and reproducible research results. Several quality markers should be considered when evaluating peptide products:

Peptide Purity

Peptide purity refers to the percentage of the desired peptide sequence in the final product. High purity is essential to minimize the presence of unwanted side products that could interfere with research findings. Purity is typically determined by High-Performance Liquid Chromatography (HPLC) and should be at least 98% for research-grade peptides. Look for a Certificate of Analysis (CoA) from the supplier that specifies the purity level and the HPLC method used for its determination. Check the chromatogram for any significant impurity peaks. A purity level of 99% or higher is preferred, especially for sensitive research applications.

Practical Tip: Request a representative HPLC chromatogram from the supplier before purchasing. Examine the chromatogram carefully to assess the presence of any significant impurity peaks. Be wary of suppliers who are unwilling to provide this information.

Peptide Identity

Peptide identity confirms that the product is indeed the intended peptide sequence. Mass spectrometry (MS) is the gold standard for verifying peptide identity. The mass spectrum should show a peak corresponding to the expected molecular weight of the peptide. The supplier should provide MS data as part of the CoA.

Practical Tip: Compare the experimentally determined molecular weight from the MS data with the theoretical molecular weight of the peptide. Small deviations may be acceptable (e.g., within +/- 1 Dalton), but larger discrepancies should raise concerns.

Peptide Content

Peptide content refers to the actual amount of peptide present in the vial, taking into account factors such as water content and counter-ion content (e.g., acetate). This is typically expressed as a percentage of the total weight of the peptide product. Peptide content is crucial for accurate dosing. Amino acid analysis (AAA) is often used to determine peptide content. The CoA should specify the peptide content and the method used for its determination.

Practical Tip: Pay close attention to the peptide content, as it can vary significantly between different suppliers. A lower peptide content means that you will need to use more of the product to achieve the desired dose.

Water Content

Peptides are hygroscopic and can absorb water from the atmosphere. Excessive water content can affect the accuracy of dosing and the stability of the peptide. Karl Fischer titration is the standard method for determining water content. The water content should ideally be less than 5%.

Counter-ion Content

During peptide synthesis and purification, counter-ions (e.g., acetate) are often introduced. These counter-ions contribute to the overall weight of the peptide product and need to be accounted for in dosing calculations. The CoA should specify the type and amount of counter-ion present.

Amino Acid Analysis (AAA)

AAA is a quantitative method for determining the amino acid composition of the peptide. It can be used to verify the sequence and purity of the peptide. The results should match the expected amino acid ratios for the intended sequence.

Endotoxin Levels

Endotoxins are bacterial toxins that can contaminate peptide products and cause adverse reactions in research animals. The Limulus Amebocyte Lysate (LAL) assay is used to measure endotoxin levels. Endotoxin levels should be as low as possible, ideally less than 10 EU/mg (Endotoxin Units per milligram) for research use.

Common Impurities

Several impurities can be present in peptide products. These impurities can arise from incomplete synthesis, side reactions, or degradation during storage. Common impurities include:

• Deletion Sequences: Peptides missing one or more amino acids.
• Truncated Sequences: Peptides with a shorter sequence than the intended peptide.
• Modified Amino Acids: Amino acids that have undergone unwanted modifications (e.g., oxidation, deamidation).
• Diastereomers: Peptides with incorrect stereochemistry at one or more chiral centers.
• Aggregates: Peptides that have formed aggregates, which can affect their solubility and biological activity.

High-quality peptide suppliers will employ purification techniques to minimize the presence of these impurities. HPLC and MS are used to identify and quantify impurities.

Storage Requirements

Proper storage is essential to maintain the stability and integrity of CJC-1295 peptides. The following storage recommendations should be followed:

• Lyophilized Peptides: Store lyophilized peptides at -20°C or lower. Protect from moisture and light.
• Reconstituted Peptides: Reconstitute peptides with sterile water or a suitable buffer. Store reconstituted peptides at 4°C for short-term storage (up to one week) or at -20°C for long-term storage. Avoid repeated freeze-thaw cycles.
• Protect from Light: Store peptides in amber vials or wrap them in aluminum foil to protect them from light.
• Minimize Exposure to Air: When handling peptides, minimize their exposure to air to prevent oxidation.

Practical Tip: Aliquot reconstituted peptides into smaller volumes to avoid repeated freeze-thaw cycles. This will help to maintain their stability and activity.

CJC-1295 With and Without DAC: A Comparison Table

Sourcing Considerations

Sourcing high-quality CJC-1295 peptides can be challenging. Here are some factors to consider when choosing a supplier:

• Reputation and Experience: Choose a supplier with a proven track record and a reputation for quality.
• Certificate of Analysis (CoA): Ensure that the supplier provides a comprehensive CoA for each batch of peptide. The CoA should include data on purity, identity, peptide content, water content, counter-ion content, and endotoxin levels.
• Manufacturing Practices: Inquire about the supplier's manufacturing practices. Do they follow Good Manufacturing Practices (GMP)?
• Customer Support: Choose a supplier that offers excellent customer support and is responsive to your questions.
• Independent Testing: Consider sending samples to an independent laboratory for testing to verify the supplier's claims.

Practical Tip: Before placing a large order, purchase a small sample of the peptide to test its quality and purity. This will help you to avoid wasting money on a substandard product.

Key Takeaways

• CJC-1295 is a GHRH analog used to stimulate GH release in research settings.
• CJC-1295 exists in two main forms: with and without DAC, differing primarily in their half-life and GH release patterns.
• Mod GRF 1-29 (without DAC) has a short half-life, leading to pulsatile GH release.
• CJC-1295 with DAC has a long half-life, leading to sustained GH elevation.
• Essential quality markers include purity (?98% by HPLC), identity (verified by MS), peptide content, water content, counter-ion content, and endotoxin levels (?10 EU/mg).
• Common impurities include deletion sequences, truncated sequences, and modified amino acids.
• Store lyophilized peptides at -20°C or lower, protected from moisture and light. Reconstituted peptides should be stored at 4°C (short-term) or -20°C (long-term), avoiding repeated freeze-thaw cycles.
• Carefully evaluate suppliers based on their reputation, CoA availability, manufacturing practices, and customer support.