PEG MGF 5 mg

One-Peptides PEG-MGF 5 mg

PEG-MGF (PEGylated mechano-growth factor) PEGylated Mechano Growth Factor) offered by One-Peptides in a package containing 5 mg of lyophilized powder is a chemical reagent intended only for research applications (Research Use Only, RUO). The product is not a medicine, dietary supplement or substance approved for use outside a laboratory environment. The classification results from the provisions of Art. 3a of the Pharmaceutical Law and the guidelines of the Chief Sanitary Inspectorate.

The history of the discovery of MGF dates back to the 1990s and is associated with the work of Geoffrey Goldspink’s team from University College London. Goldspink and colleagues identified MGF as a splice variant of the IGF-1 gene that arises specifically in response to mechanical stress on muscle tissue. This discovery changed the current understanding of IGF-1 signaling, revealing that the same gene can generate isoforms with different – or even opposing – biological functions in the context of satellite cell regulation.

PEGylation, i.e. the covalent conjugation of a peptide with polyethylene glycol (PEG), is a widely used post-translational modification in the chemistry of research peptides, aimed at extending the biological half-life of the molecule by reducing proteolytic degradation and renal clearance.

General description of PEG-MGF

In laboratory practice, this reagent is often compared with CJC-1295 WITH DAC 5 mg and TB-500 5 mg, to assess differences in performance profile across consistent study protocols.

MGF (Mechano Growth Factor) belongs to the superfamily of insulin-like growth factors – a group of signal peptides of fundamental importance in stem cell biology, tissue regeneration and mitogenic signaling. As a splice variant of IGF-1 (specifically isoform IGF-1Ec in humans, IGF-1Eb in rodents), MGF possesses a unique C-terminal extension peptide (E-peptide), which distinguishes it from canonical IGF-1 isoforms (IGF-1Ea).

The interest of the scientific community in MGF results from several observations made in cellular and animal models: (1) MGF is formed only in response to a mechanical stimulus or tissue damage, (2) it activates satellite cells (skeletal muscle stem cells) without promoting their differentiation, (3) it has biological activity independent of the classical IGF-1R receptor. These features make MGF an interesting tool for studying the early stages of tissue regeneration at the cellular level.

What is PEG-MGF?

PEG-MGF is a PEGylated form of the C-terminal MGF peptide with the sequence: YQPPSTNKNTKSQRRKGSTFEEHK (24 amino acids), covalently conjugated to a polyethylene glycol (PEG) chain.

Molecular parameters of the MGF peptide (before PEGylation)

Sequence: YQPPSTNKNTKSQRRKGSTFEEHK

Peptide molecular weight: ~2867 g/mol

Number of amino acids: 24

Molecular weight of the PEGylated form: depends on the size of the PEG chain used (typically PEG weighing 2–5 kDa), giving a total mass in the range of ~5–8 kDa

It is worth emphasizing that this 24-amino acid C-terminal peptide is a fragment unique to the IGF-1Ec isoform – it does not occur in any other IGF-1 isoform. It is this sequence that is responsible for the biological properties that distinguish MGF from classic IGF-1.

Biochemical classification

In terms of classification, MGF is classified as:
– Growth factors from the IGF superfamily
– Signal peptides regulating stem cell proliferation
– Splicing variants with tissue specificity of expression

MGF is not an independent gene – it is encoded by the same gene IGF1, but is formed as a result of alternative pre-mRNA splicing, in which exon 5 (in rodents) or exon 6 (in humans) is included, generating a unique Ec domain.

Structure and physicochemical properties

Structure of the PEG-MGF peptide

The YQPPSTNKNTKSQRRKGSTFEEHK sequence contains several structural features important for biological activity:

• Proline-rich region (YQPP-): N-terminal fragment with two proline residues giving local stiffness to the peptide chain and promoting type II polyproline structures (PPII)
• Base Region (SQRRK): a concentration of arginine and lysine residues with a net positive charge, potentially responsible for interactions with negatively charged proteoglycans of the extracellular matrix
• C-terminal region (STFEEHK): contains acidic residues (Glu-Glu) balancing the positive charge of the base region; a His residue at the C-terminus confers pH sensitivity

Studies using circular dichroism (CD) and NMR methods indicate that the MGF peptide in aqueous solution does not assume a stable secondary structure – it is largely unstructured (intrinsically disordered), which is a feature common to many signal peptides that interact with multiple protein partners.

PEGylation – chemical aspects

Covalent attachment of the PEG chain to the MGF peptide is most often carried out by:
– N-terminal amino acids — modification of the alpha-amino group of Tyr1
– Lysine side chains — Lys8, Lys12, Lys24 are potential PEGylation sites
– C-end — less frequently used due to proximity to the functional region

PEGylation introduces several physicochemical changes:
1. Increase in molecular weight — from ~2.9 kDa to ~5–8 kDa (depending on PEG mass)
2. Increased hydrodynamic radius — PEG forms a hydrated “cloud” around the peptide, which reduces the availability of proteases
3. Decreased renal clearance — larger particle size lowers glomerular filtration
4. Solubility modification — PEG improves solubility in aqueous media

Solubility and stability

The freeze-dried form of PEG-MGF shows good stability at -20 °C. The peptide dissolves in distilled water, saline solutions and dilute acetic acid (0.1%). The stability of the working solution at 4 °C is approximately 48-72 hours; For long-term storage, aliquoting and freezing at -80 °C is recommended.

The main degradation pathways include: deamidation of Asn and Gln residues, oxidation of Tyr, and hydrolysis of the PEG-peptide bond under extreme pH conditions.

Mechanism of action at the molecular level

IGF-1R-independent signaling

One of the most intriguing aspects of MGF biology is the observation that the C-terminal Ec peptide exhibits biological activity independent of the classical IGF-1 receptor (IGF-1R). Studies on cell cultures using IGF-1R blocking antibodies and IGF-1R tyrosine kinase inhibitors (e.g. NVP-AEW541) have shown that the MGF peptide retains the ability to activate satellite cell proliferation even in conditions of full IGF-1R blockade.

This IGF-1R-independent mechanism has not yet been fully characterized at the receptor level. Research hypotheses include:
– Interactions with an unidentified Ec domain-specific surface receptor
– Peptide internalization and direct interaction with intracellular pathways
– Interactions with extracellular matrix proteoglycans modulating the local availability of growth factors

MAPK/ERK trail

Regardless of the unidentified receptor, MGF peptide activates the MAPK/ERK (MAP kinase/extracellular signal-regulated kinase) pathway in C2C12 satellite cells and myoblasts:

1. Ras activation (details of the upstream mechanism are not fully understood)
2. Raf cascade phosphorylation –> MEK1/2 –> ERK1/2
3. Translocation of phospho-ERK1/2 into the cell nucleus
4. Activation of transcription factors promoting proliferation (c-Fos, c-Jun)

Studies using a MEK1/2 inhibitor (U0126 or PD98059) blocked myoblast proliferation induced by the MGF peptide, confirming the central involvement of the ERK pathway in the mechanism of action.

Difference between MGF and IGF-1: proliferation vs. differentiation

The fundamental difference between MGF and canonical IGF-1 isoforms concerns their effect on satellite cell fate:

• IGF-1 (IGF-1Ea isoforms): activates both proliferation and – in later phases – differentiation of myoblasts, leading to fusion into multinucleated myotubes. Dominant pathway: PI3K/Akt/mTOR
• MGF (IGF-1Ec isoform, C-terminal peptide): preferentially maintains satellite cells in a proliferative state without promoting differentiation. Dominant pathway: MAPK/ERK

This dichotomy has important research implications: it suggests that there is a two-step mechanism in the process of muscle tissue regeneration – an early phase of satellite cell expansion (regulated by MGF) and a late phase of differentiation and fusion (regulated by canonical IGF-1). Observations from muscle injury models in Wistar rats support this sequence – MGF mRNA expression appears early (within 24-48 hours after injury) and declines rapidly, whereas IGF-1Ea expression increases later (3-7 days).

Applications in scientific research

C2C12 myoblast cultures

The C2C12 cell line (mouse myoblasts) is a basic in vitro model for studying MGF activity. Exposure of C2C12 cultures to MGF peptide at nanomolar concentrations leads to:
– Increased proliferation assessed by the MTT or BrdU test
– Delays in differentiation measured by myogenin and MHC (myosin heavy chain) expression
– Activation of ERK1/2 phosphorylation (Western blot, immunofluorescence)

The PEGylated form of the peptide allows experiments with prolonged exposure time without the need to frequently replace the medium – the reduction of proteolytic degradation by PEG allows maintaining a stable working concentration in the culture environment.

Satellite cell models

Primary cultures of satellite cells isolated from rodent skeletal muscles (Wistar rats, C57BL/6 mice) constitute a more physiological model than the C2C12 line. In these cultures, the MGF peptide activates satellite cells in the quiescent state (Pax7+/MyoD- expression), inducing their entry into the cell cycle (Pax7+/MyoD+ state) without immediately entering the differentiation phase (Pax7-/myogenin+).

This observation is particularly important in the context of research on stem cell depletion – the ability to expand the population of satellite cells without losing their stem cell potential is the subject of intense research.

Models of muscle tissue regeneration in rodents

In models of skeletal muscle damage (cryotoxin, cardiotoxin, BaCl2) in Wistar rats and C57BL/6 mice, the kinetics of endogenous MGF expression are analyzed by RT-qPCR and immunohistochemistry. These studies allow the correlation of MGF expression with the proliferative phase of regeneration (number of BrdU+ cells, PCNA expression) and the assessment of the impact of exogenous MGF peptide on the dynamics of this process.

Peptide PEGylation is particularly important in in vivo models – unmodified MGF peptide undergoes rapid proteolytic degradation (half-life of the order of minutes), which limits research possibilities. The PEGylated form extends the presence of the active peptide, allowing the effects to be observed in longer time windows.

Cardiac progenitor cell models

MGF peptide is also studied in the context of cardiac progenitor cells (CPC, cardiac progenitor cells). CPC cultures exposed to MGF peptide show an increase in proliferation and modulation of the expression of stem cell markers (c-kit, Sca-1). These observations are under investigation in the context of cardiac tissue regeneration after ischemic injury in animal models.

Mechanotransduction studies

MGF, as a mechanically induced peptide, is a tool for studying mechanotransduction pathways – the processes of transforming mechanical stimuli into biochemical signals. Experiments using cyclic stretching of myoblasts on flexible membranes (Flexcell systems) allow the correlation of the intensity of the mechanical stimulus with the level of MGF expression and the activation of downstream signaling pathways.

Summary

PEG-MGF 5 mg from One-Peptides is a research reagent containing a PEGylated form of the 24-amino acid C-terminal peptide of the IGF-1Ec isoform (Mechano Growth Factor). This molecule – with a peptide mass of ~2867 g/mol, increased by the covalently attached PEG chain – stands out in the IGF superfamily for its ability to activate satellite cell proliferation without promoting differentiation, its action independent of the IGF-1R receptor and the preferential activation of the MAPK/ERK pathway.

The product is intended for research use only (Research Use Only). It is not a medicine or food. All data presented in this description comes from published scientific research and does not constitute claims about health properties.

Research conclusions

• MGF is a splice variant of IGF-1 (IGF-1Ec isoform) produced specifically in response to mechanical stress on the tissue.
• The C-terminal MGF peptide (24 aa) shows biological activity independent of the classical IGF-1R receptor – the receptor mechanism remains the subject of research
• In cultured C2C12 myoblasts and primary satellite cells, MGF peptide activates proliferation via the MAPK/ERK pathway without promoting differentiation — unlike canonical IGF-1 isoforms
• PEGylation increases the biological half-life of the peptide, enabling studies requiring prolonged exposure in cellular and animal models
• Endogenous MGF expression in rodent models of muscle regeneration appears early (24-48 h after injury) and precedes IGF-1Ea expression, suggesting a role in the initiation of the proliferative phase of regeneration.

Literature context: see the overview research on PEG-MGF in the context of laboratory research and RUO framing.