IGF-1 LR3 research centres on a 83-residue analogue of insulin-like growth factor I engineered to evade the IGF-binding proteins that sequester the native hormone. Alongside it sit IGF-1 DES(1-3), a truncated variant with the same design goal, and MGF and PEG-MGF, synthetic versions of the E-domain peptide produced by a mechanically induced splice variant of the IGF1 gene. This guide sets out the structural differences, verified identity data and laboratory handling for all four.
Key takeaways
- IGF-1 LR3 carries two changes relative to native IGF-1: an Arg-for-Glu substitution at position 3 and a 13-residue N-terminal extension (MFPAMPLLSLFVN), giving 83 residues and a molecular weight of 9117.6 Da.
- IGF-1 DES(1-3) takes the opposite approach — it deletes the first three residues of IGF-1, leaving 67 residues and a molecular weight of 7371.5 Da.
- Both modifications target the same problem: the IGF-binding proteins. Bach’s 2018 review sets out how the six IGFBPs control IGF availability in circulation and tissue.
- Tomas and colleagues reported in Biochemical Journal (1993) that IGF-I variants with reduced binding-protein affinity restored growth in diabetic rats more effectively than native IGF-I.
- MGF is the 24-residue C-terminal E-domain peptide of the IGF-1Ec splice variant, sequence YQPPSTNKNTKSQRRKGSTFEERK, MW 2868.2 Da. It is not IGF-1 and does not carry the IGF-1 receptor-binding domain.
- Yang and Goldspink reported in FEBS Letters (2002) that the IGF-I Ec peptide and mature IGF-I had different effects on myoblast proliferation and differentiation in culture.
- PEG-MGF is MGF with a polyethylene glycol chain attached, a stability modification intended to slow clearance of a peptide reported to be rapidly metabolised.
What is IGF-1 LR3?
IGF-1 LR3 (Long R3 IGF-1) is a recombinant analogue of human insulin-like growth factor I built to retain IGF-1 receptor agonism while binding poorly to the IGF-binding proteins. It is 83 amino acids long against IGF-1’s 70, with molecular formula C400H625N111O115S9 and a molecular weight of 9117.6 Da.
The name encodes the chemistry. “R3” is the arginine substituted for glutamate at position 3, the residue that contributes most to IGFBP contact. “Long” is the 13-residue extension added at the N-terminus, which further reduces binding-protein recognition and improves recombinant expression.
In the published literature the analogue is reported as roughly three times more potent than native IGF-1 on a molar basis, with a longer measured half-life. Both properties follow from the same cause: more of the molecule is free rather than bound.
The GH–IGF axis and where each compound sits
Growth hormone released from the pituitary acts on hepatocytes to induce IGF-1, and circulating IGF-1 feeds back to restrain further GH release. That endocrine loop is only half the system: IGF-1 is also produced locally in muscle, bone and other tissues, where it acts in an autocrine and paracrine fashion.
The four compounds in this guide split cleanly across that divide. LR3 and DES(1-3) are analogues of the mature, receptor-binding IGF-1 molecule. MGF and PEG-MGF are the E-domain peptide from a locally expressed splice variant — a different molecule with a different proposed mode of action.
Steyn and colleagues cover the upstream regulation of this axis in Comprehensive Physiology; Bach’s 2018 review covers the binding-protein layer that sits between the liver and the receptor.
Why IGF-binding proteins drive the chemistry
The short answer: almost none of the IGF-1 in circulation is free. Six high-affinity IGF-binding proteins bind IGF-1 and IGF-2, and most circulating IGF-1 travels in a ternary complex with IGFBP-3 and the acid-labile subunit. That complex is too large to leave the vascular compartment readily, so the binding proteins act as both a reservoir and a brake.
Every analogue in this guide except MGF exists because of that brake. Reduce IGFBP affinity and the same molar quantity of peptide delivers more receptor occupancy — the finding Tomas and colleagues reported in diabetic rats, where IGF-I variants that bind binding-proteins poorly restored growth more effectively than native IGF-I.
IGF-1 LR3: structure and design rationale
Native IGF-1 is a single 70-residue chain with three intramolecular disulfide bonds, structurally homologous to proinsulin. IGF-1 LR3 modifies it in two places.
The Arg3 substitution
Position 3 of IGF-1 is glutamate, a negatively charged residue in the N-terminal region that participates in IGFBP contact. Replacing it with arginine reverses the charge at that position and markedly reduces binding-protein affinity while leaving the receptor-binding surface intact.
The 13-residue N-terminal extension
The “Long” prefix refers to the sequence MFPAMPLLSLFVN added ahead of residue 1. It contributes further to IGFBP evasion and serves a practical purpose in recombinant production. The combined result is an 83-residue protein reported to have very low IGFBP affinity and approximately threefold the potency of native IGF-1.
IGF-1 DES(1-3): truncation instead of extension
IGF-1 DES(1-3) removes the first three residues of IGF-1 — the tripeptide Gly-Pro-Glu — leaving a 67-residue protein of formula C319H501N91O96S7 and molecular weight 7371.5 Da, listed under CAS 112603-35-7.
The deletion removes Glu3 entirely rather than substituting it, and the published characterisation describes considerably reduced binding to the IGFBPs with markedly enhanced in-vivo potency relative to IGF-1. DES(1-3) also occurs naturally as a proteolytic product in some tissues, which makes it a physiologically relevant fragment as well as a research reagent.
The practical difference between LR3 and DES(1-3) in a laboratory setting is mass, not concept. Both strip the same N-terminal recognition element; DES(1-3) is the smaller of the two by roughly 1750 Da.
MGF: the IGF-1Ec splice variant E-domain
Mechano growth factor is a different kind of molecule. The IGF1 gene can be spliced into several transcripts; the IGF-1Ec variant in humans is expressed in muscle after mechanical loading and damage. Post-translational cleavage separates the mature IGF-1 portion from a distinct C-terminal E-domain peptide, and it is that 24-residue peptide that is sold as MGF.
Its sequence is YQPPSTNKNTKSQRRKGSTFEERK, formula C121H199N41O40, molecular weight 2868.2 Da. Critically, it does not contain the IGF-1 receptor-binding surface. Whatever MGF does in the published literature, it is not doing it as an IGF-1 receptor agonist.
Yang and Goldspink reported in FEBS Letters in 2002 that the IGF-I Ec peptide and mature IGF-I had distinguishable effects on myoblast proliferation and differentiation in culture — the observation on which most subsequent MGF research is built.
PEG-MGF: why the polymer is attached
The native E-domain peptide is reported to be rapidly metabolised, which limits its usefulness as a research reagent in any system with active proteases. PEG-MGF attaches a polyethylene glycol chain to the peptide to increase hydrodynamic radius and slow both renal clearance and proteolytic attack.
PEGylation is a well-established protein-chemistry strategy rather than anything specific to this peptide. The practical consequences for a laboratory are three: the nominal mass on the certificate of analysis reflects peptide content rather than total conjugate mass, PEG chains are polydisperse so mass spectrometry shows a distribution rather than a single sharp peak, and solubility behaviour differs from the unmodified peptide.
Specifications and verified identity data
The four compounds span a mass range from 2868 Da to 9118 Da. Any protocol expressed in molar units needs the correct figure for the specific item, and PEG-MGF requires an additional decision about whether the concentration refers to peptide content or total conjugate.
| Compound | CAS | Formula | MW (Da) | Residues | Relationship to IGF-1 |
|---|---|---|---|---|---|
| IGF-1 (native, reference) | — | — | ~7649 | 70 | The parent hormone |
| IGF-1 LR3 | 143045-27-6 | C400H625N111O115S9 | 9117.6 | 83 | Arg3 + 13-residue N-terminal extension |
| IGF-1 DES(1-3) | 112603-35-7 | C319H501N91O96S7 | 7371.5 | 67 | N-terminal Gly-Pro-Glu deleted |
| MGF | — | C121H199N41O40 | 2868.2 | 24 | E-domain of the IGF-1Ec splice variant |
| PEG-MGF | — | MGF + PEG | 2868.2 peptide portion | 24 + polymer | PEGylated E-domain peptide |
| Property | IGF-1 LR3 | IGF-1 DES(1-3) | MGF | PEG-MGF |
|---|---|---|---|---|
| Binds IGF-1 receptor | Yes | Yes | No receptor-binding domain | No receptor-binding domain |
| IGFBP affinity | Very low | Considerably reduced | Not applicable | Not applicable |
| Reported potency vs IGF-1 | ~3× (molar) | ~10× in vivo | Not comparable | Not comparable |
| Stability strategy | Sequence engineering | Sequence truncation | None | PEG conjugation |
| Disulfide bonds | 3 | 3 | None | None |
| Typical vial size | 1 mg | 2 mg | 2 mg | 2 mg |
| Class label | IGF analogue | IGF analogue | E-domain peptide | E-domain peptide |
Handling, reconstitution and stability
IGF-1 LR3 and IGF-1 DES(1-3) are folded proteins with three disulfide bonds, not short synthetic peptides. That changes the handling requirements: they are more sensitive to shear, surface adsorption and pH extremes than a hexapeptide, and denaturation is irreversible.
- Choose the diluent deliberately. Disulfide-containing IGF analogues are commonly reconstituted in dilute acetic acid or a defined buffer rather than plain water; check the batch documentation before assuming bacteriostatic water is appropriate.
- Add the diluent down the vial wall. Never onto the lyophilised cake directly, and never with force.
- Do not vortex. Swirl gently until dissolved. Air-liquid interface exposure denatures folded proteins.
- Carrier protein for dilute stocks. At low concentrations, IGF analogues adsorb to plastic; a carrier such as 0.1 % bovine serum albumin is standard practice in cell-culture work where compatible with the assay.
- Aliquot immediately. Freeze-thaw cycling is the main practical cause of activity loss in this class.
- Record the mass basis for PEG-MGF. State on every label whether the concentration refers to peptide content or total conjugate.
| Mass in vial | Diluent | Concentration | Per 0.1 mL | Molarity if MGF (2868.2) | Molarity if LR3 (9117.6) |
|---|---|---|---|---|---|
| 1 mg | 1 mL | 1 mg/mL | 100 mcg | 349 µM | 110 µM |
| 1 mg | 2 mL | 0.5 mg/mL | 50 mcg | 174 µM | 55 µM |
| 2 mg | 1 mL | 2 mg/mL | 200 mcg | 697 µM | 219 µM |
| 2 mg | 2 mL | 1 mg/mL | 100 mcg | 349 µM | 110 µM |
| 2 mg | 4 mL | 0.5 mg/mL | 50 mcg | 174 µM | 55 µM |
Limitations of the published evidence
The IGF-1 analogue literature is stronger than the MGF literature. LR3 and DES(1-3) have decades of published in-vitro and animal pharmacology, and their reduced-IGFBP design is well characterised. What that literature does not provide is evidence for any specific applied outcome; the studies are mechanistic.
MGF research is more contested. The molecule has no IGF-1 receptor-binding domain, and a receptor for the E-domain peptide has not been definitively established. Reported effects on progenitor and satellite cells are real observations in specific systems, but the mechanism remains an open question rather than a settled one.
PEG-MGF adds a further layer. Because PEG chains are polydisperse and PEGylation site can vary between preparations, results obtained with one preparation may not transfer directly to another. Batch-level characterisation matters more here than for a defined small peptide.
IGF and MGF peptides in the GenoPept store
Frequently asked questions
What does the LR3 in IGF-1 LR3 actually stand for?
It encodes the two modifications. The R3 refers to arginine substituted for the native glutamate at position 3, and Long refers to a 13-residue extension (MFPAMPLLSLFVN) added at the N-terminus. Together they give an 83-residue protein of 9117.6 Da that binds the IGF-binding proteins far more weakly than native IGF-1 does.
What is the difference between IGF-1 LR3 and IGF-1 DES(1-3)?
Both reduce IGF-binding-protein affinity by altering the same N-terminal region, but in opposite directions. LR3 substitutes arginine at position 3 and adds 13 residues, giving 83 residues and 9117.6 Da. DES(1-3) deletes the first three residues instead, giving 67 residues and 7371.5 Da. LR3 is reported at roughly threefold IGF-1 potency; DES(1-3) at around tenfold in vivo.
Is MGF a form of IGF-1?
No. MGF is the 24-residue C-terminal E-domain peptide produced when the IGF-1Ec splice variant is post-translationally cleaved. It is a separate molecule of 2868.2 Da that does not carry the IGF-1 receptor-binding surface, so it cannot act as an IGF-1 receptor agonist. Mature IGF-1, by contrast, is a 70-residue protein of roughly 7649 Da.
Why is MGF PEGylated?
The unmodified E-domain peptide is reported to be rapidly metabolised, which limits its useful window in any system with active proteases. Attaching a polyethylene glycol chain increases the molecule’s hydrodynamic radius, slowing renal filtration and sterically hindering proteolytic attack. PEGylation is a general protein-chemistry technique rather than anything specific to this peptide.
Why do IGF-binding proteins matter so much in this class?
Because they control how much IGF-1 is actually free to reach a receptor. Six high-affinity binding proteins bind IGF-1 and IGF-2, and most circulating IGF-1 travels in a ternary complex with IGFBP-3 and the acid-labile subunit. Every analogue in this guide except MGF exists to reduce that sequestration.
Should IGF-1 LR3 be reconstituted with bacteriostatic water?
Not automatically. IGF-1 LR3 and IGF-1 DES(1-3) are folded proteins with three disulfide bonds, and they are commonly reconstituted in dilute acetic acid or a defined buffer rather than plain water. Check the batch documentation for the recommended diluent before preparing a stock, and never vortex a folded-protein solution.
Why does PEG-MGF give a broad peak on mass spectrometry?
Polyethylene glycol chains are polydisperse — a preparation contains a distribution of chain lengths rather than one exact mass. A PEGylated peptide therefore produces a cluster of masses spaced by the repeat unit instead of a single sharp signal. Certificates of analysis for PEG conjugates usually report peptide content separately from total mass.
Do these compounds need carrier protein in solution?
Dilute IGF analogue solutions adsorb measurably to plastic surfaces, which can reduce the effective concentration well below the nominal figure. Where the assay allows it, a carrier such as 0.1 % bovine serum albumin is standard practice for working dilutions. Concentrated stock solutions are less affected.
References
- Bach LA. 40 YEARS OF IGF1: IGF-binding proteins. Journal of Molecular Endocrinology. 2018;61(1):T11–T28. Journal of Molecular Endocrinology
- Tomas FM, et al. Insulin-like growth factor-I and more potent variants restore growth of diabetic rats without inducing all characteristic insulin effects. Biochemical Journal. 1993;291(3):781–786. Biochemical Journal
- Yang SY, Goldspink G. Different roles of the IGF-I Ec peptide (MGF) and mature IGF-I in myoblast proliferation and differentiation. FEBS Letters. 2002;522(1–3):156–160. FEBS Letters
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. The Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799–805. PubMed
- Steyn FJ, Tolle V, Chen C, Epelbaum J. Neuroendocrine regulation of growth hormone secretion. Comprehensive Physiology. 2016;6(2):687–735. Wiley
Research-grade IGF-1 LR3, DES(1-3), MGF and PEG-MGF
GenoPept supplies IGF-1 LR3, IGF-1 DES(1-3), MGF and PEG-MGF as lyophilised vials with a per-batch third-party certificate of analysis covering HPLC purity and mass confirmation, dispatched from the UK strictly for laboratory research.