IGF1-LR3

Overview

IGF1-LR3 — Long R³ insulin-like growth factor 1 — is an engineered analogue of human IGF-1, studied in research on cell growth, protein synthesis and metabolic signalling.

It is the largest molecule in this catalogue by a considerable margin, and the only one that is not made by chemical synthesis. Both facts matter more than they might sound.

Chemical identity

• Also known as: Long R³ IGF-1, LR3-IGF-1
• CAS number: 143045-27-6
• Molecular formula: C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉
• Molecular weight: approximately 9117.6 g/mol
• Classification: Recombinant IGF-1 analogue
• Length: 83 residues
• Appearance: White lyophilised powder

The molecular weight is given as approximate for a reason that recurs throughout this page: this is a recombinant protein, and recombinant preparations are characterised as populations rather than as single exact species in the way a synthetic peptide is.

The nine sulfur atoms are cysteines and methionines. The cysteines form disulphide bonds that hold the protein in its active three-dimensional shape — which, unlike every short peptide in this catalogue, it genuinely has.

What IGF-1 is, and why it is regulated

Insulin-like growth factor 1 is a 70-residue protein produced mainly by the liver in response to growth hormone. It mediates most of growth hormone’s anabolic effects, and it is structurally related to insulin — hence the name, and hence some overlap in what their receptors do.

The important feature for understanding this compound is that IGF-1 does not circulate freely. Over 95% of it is bound to IGF-binding proteins, principally IGFBP-3, which hold it inactive and release it in a controlled way. Only the small free fraction can reach receptors.

That binding system is not an inconvenience: it is the regulation. It buffers IGF-1 levels, extends its circulating lifetime, and controls where and when it acts.

Two modifications, one purpose

IGF1-LR3 differs from native IGF-1 in two ways, and both serve the same end — escaping that regulation.

• The R³ substitution. Glutamate at position 3 is replaced by arginine. That position matters for binding-protein affinity, and the substitution substantially reduces it.
• The “Long” extension. A 13-residue peptide is added to the N-terminus, further reducing binding-protein association.

The result is a molecule that binds the IGF-1 receptor much as native IGF-1 does but is largely invisible to the proteins that would otherwise sequester it. Reported half-life is on the order of many hours against roughly ten minutes for the free native protein.

It is worth being clear about what that means. The compound is not more potent at the receptor; it is less regulated. It bypasses a control system rather than pushing harder on the signal — a distinction that matters for interpreting any result obtained with it, since the biology being observed is partly the absence of normal restraint.

Related compounds here

IGF1-DES is a different modification of the same parent protein, taking the opposite structural approach — a truncation rather than an extension — toward a similar end.

The GHRH analogues and secretagogues elsewhere in this catalogue relate to IGF-1 indirectly: Mod GRF 1-29 and GHRP-6 raise growth hormone, which raises IGF-1 through the liver. Those compounds work upstream, within the axis and its feedback. This one is the downstream product supplied directly, with the feedback bypassed.

Recombinant, not synthesised

Every other compound in this catalogue is built by solid-phase peptide synthesis: amino acids coupled one at a time onto a resin. That approach becomes impractical somewhere around fifty residues, and at 83 residues with disulphide bonds requiring correct folding, it is not a realistic route.

IGF1-LR3 is instead produced by recombinant expression — the gene is introduced into a host organism, usually a bacterium or yeast, which manufactures the protein. It is then purified from that culture and refolded.

This changes what can go wrong, completely:

• Folding. A synthetic peptide is either the right sequence or not. A recombinant protein can have exactly the right sequence and mass while being folded incorrectly — and a misfolded protein has the wrong shape, so it does not bind its receptor. Mass spectrometry cannot detect this.
• Host cell impurities. Proteins and DNA from the expression organism, which have no counterpart in synthetic production.
• Endotoxin. Bacterial expression brings lipopolysaccharide from the host cell wall, which is biologically active at very low concentrations and is a standard concern for any bacterially produced protein.
• Aggregation. Proteins can clump into inactive aggregates during purification or storage in ways short peptides do not.

Handling, reconstitution and storage

Protein handling is more demanding than peptide handling, and for structural reasons.

• Structure can be lost without the molecule being destroyed. This is the key difference. A denatured protein has intact covalent bonds and correct mass, and no activity. Heat, extreme pH, and mechanical stress all cause it.
• Never shake. This applies to every peptide here and applies far more forcefully to a folded protein. Foaming at an air-liquid interface unfolds proteins efficiently.
• Avoid reducing agents. Disulphide bonds hold the fold together; DTT, beta-mercaptoethanol or TCEP will open them and unfold the protein.
• Freeze–thaw cycles are more damaging than for short peptides. Aliquot rather than repeatedly refreezing.
• Lyophilised storage: sealed, frozen for anything beyond short-term.
• Reconstitution: add diluent slowly down the vial wall and allow it to dissolve without agitation. Do not vortex.
• Concentration: our reconstitution calculator handles the arithmetic; note the molecular weight is far higher than the peptides, so quantities differ.

Purity and analytical verification

This is the compound where a standard peptide certificate tells you least, and it is worth understanding why before relying on one.

HPLC purity and mass confirmation are necessary but not sufficient. They establish that the material is the right sequence at the right mass. For a synthetic peptide that is close to the whole question. For a folded protein it leaves the most important question untouched: is it folded correctly? A correctly folded and a misfolded molecule are chemically identical and differ only in shape.

What actually answers that is a bioactivity assay — typically a cell-based measurement of receptor activation or proliferation. That is the test that distinguishes active protein from inactive protein of identical composition, and it is the figure worth asking for.

Two further measures are standard for recombinant proteins and absent from peptide certificates: endotoxin content, which matters for any bacterially expressed material used in cell culture, and host cell protein levels.

A certificate reporting only HPLC purity for a recombinant protein is applying peptide standards to something that is not a peptide.

We publish third-party certificates of analysis by batch.

References

• Rinderknecht E, Humbel RE. The amino acid sequence of human insulin-like growth factor I and its structural homology with proinsulin. Journal of Biological Chemistry, 1978. PMID 632300
• Francis GL, Ross M, Ballard FJ, et al. Novel recombinant fusion protein analogues of insulin-like growth factor (IGF)-I indicate the relative importance of IGF-binding protein and receptor binding for enhanced biological potency. Journal of Molecular Endocrinology, 1992. PMID 1378742
• Tomas FM, Knowles SE, Owens PC, et al. Effects of full-length and truncated insulin-like growth factor-I on nitrogen balance and tissue protein synthesis in nitrogen-restricted rats. Journal of Endocrinology, 1991. PMID 1999680

Summary

IGF1-LR3 is a recombinant analogue of insulin-like growth factor 1, CAS 143045-27-6, molecular formula C₄₀₀H₆₂₅N₁₁₁O₁₁₅S₉, molecular weight approximately 9,117.6 g/mol — 83 residues, the largest molecule in this catalogue. An arginine substitution at position 3 and a 13-residue N-terminal extension both reduce its affinity for IGF-binding proteins, so it escapes the system that normally holds IGF-1 inactive and releases it under control. It is therefore not more potent at the receptor but less regulated, which is worth remembering when interpreting results. As a recombinant protein rather than a synthetic peptide, its failure modes are folding, host cell impurities, endotoxin and aggregation — none of which a standard peptide certificate addresses.

For laboratory research use only. Not for human consumption. This material is not a drug, food, or cosmetic and may not be sold or used for any purpose other than in vitro or non-human laboratory research.