IGF-1 DES is insulin-like growth factor 1 with the first three residues of the mature chain removed. Deleting glycine, proline and glutamate from the N-terminus leaves a 67 residue protein that still binds and activates the type 1 IGF receptor while losing most of its affinity for the circulating binding proteins that normally sequester IGF-1. It occurs naturally in bovine colostrum and in some human tissue extracts, and is produced recombinantly for laboratory work.
Key facts
| Type | N-terminally truncated analogue of insulin-like growth factor 1 |
| Amino acid count | 67, against 70 in the mature parent |
| Truncation | Removal of Gly1, Pro2 and Glu3 from the mature IGF-1 chain |
| Calculated average mass | 7365 g/mol, against 7649 g/mol for intact IGF-1 |
| Disulfide bonds | Three, conserved from the parent fold |
| Binding protein affinity | Roughly one tenth to one hundredth that of intact IGF-1 |
| Receptor | Type 1 insulin-like growth factor receptor, IGF1R |
| Synonyms | DES(1-3)IGF-1, des-IGF-1, IGF-1 DES 1-3 |
Structure and chemistry
Mature human IGF-1 is a 70 residue single chain with three disulfide bonds and a fold homologous to proinsulin, organised into B, C, A and D domains. The first three residues sit on a flexible N-terminal extension outside the structured core, so removing them leaves the disulfide network and the receptor binding surface intact. The calculated average mass falls from 7649 to 7365 g/mol, a difference of 284 that corresponds to the glycine, proline and glutamate removed.
The consequence of the truncation is not structural but electrostatic. Glu3 makes a salt bridge with a basic residue in the binding site of the IGF binding proteins, and its loss removes a substantial part of that interaction. Reported affinity for IGFBP-3, the dominant carrier in serum, falls by one to two orders of magnitude, while affinity for the type 1 receptor is preserved or slightly increased. That combination is the entire point of the molecule as a reagent.
Recombinant production follows the same route as intact IGF-1, most often in Escherichia coli with refolding, and the analytical burden is the same. Three disulfides can pair incorrectly, and misfolded isomers separate from correctly folded material by reversed phase HPLC only if the gradient is developed carefully. A purity figure on this class of protein means little without a note on how folding isomers were resolved.
Mechanism of action
The type 1 IGF receptor is a preformed disulfide-linked heterotetramer with intrinsic tyrosine kinase activity. Ligand binding drives a conformational change that brings the kinase domains together for trans-autophosphorylation, creating docking sites for insulin receptor substrate proteins and SHC. From there the signal splits into the PI3K and AKT arm, which governs protein synthesis through mTORC1 and suppresses FOXO-dependent atrogene transcription, and the RAS to ERK arm associated with proliferation.
In serum or in any culture medium containing serum, most intact IGF-1 is bound to IGF binding proteins and is not available to the receptor. IGF-1 DES escapes that sequestration, so at equal molar concentration it presents far more free ligand to the receptor and produces a larger signal. In binding-protein-free buffer the two are close to equipotent. Experiments that compare them without controlling the binding protein content of the medium are measuring availability and not receptor pharmacology, which is a frequent source of inconsistent potency ratios in the literature.
Research applications
- Myoblast and fibroblast culture comparing AKT and ERK phosphorylation against intact IGF-1 in serum-containing and serum-free medium.
- IGF binding protein competition assays quantifying the affinity shift for IGFBP-1 through IGFBP-6.
- Receptor selectivity work distinguishing IGF1R from insulin receptor and hybrid receptor signalling.
- Protein synthesis and degradation readouts, including S6 kinase phosphorylation and atrogene transcript quantification.
- Refolding process development, resolving correctly folded material from disulfide isomers by RP-HPLC and peptide mapping.
- Comparative work against IGF-1 LR3 to separate the effect of N-terminal extension from N-terminal truncation.
Compounds studied around growth factor signalling sit in NuVion’s Growth Hormones category.
Handling in the laboratory
Recombinant IGF-1 analogues are supplied lyophilised, often from a dilute acid or a volatile buffer. Reconstitution is with sterile or bacteriostatic water run slowly down the wall of the vial and swirled, never shaken; a three disulfide protein foamed at an air interface loses activity without any visible change to the solution. The reconstitution calculator converts vial content and diluent volume into a stock concentration.
Carrier-free protein at low concentration adsorbs to plastic, so working dilutions are made in buffer containing bovine serum albumin unless the assay forbids it. Reducing agents open the disulfide network and destroy the fold, so buffers are checked before use. Material is aliquoted at first reconstitution and held frozen, since repeated freeze and thaw cycles aggregate the protein and shift the apparent potency between experiments.
Testing and supply from NuVion
NuVion supplies IGF-1 LR3, the long arginine 3 analogue that addresses the same binding protein problem from the opposite direction, together with HGH and the secretagogue range across the growth hormone axis. That range is manufactured at a GMP-audited facility and independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity confirmed by mass spectrometry, and the certificates are published in the Certificate of Analysis library. IGF-1 DES is not part of the current catalogue and this page is a reference profile.
Related compounds
The closest comparison is IGF-1 LR3, which adds a thirteen residue N-terminal extension and substitutes arginine at position 3 to achieve a similar reduction in binding protein affinity. Upstream, HGH drives hepatic IGF-1 transcription and CJC-1295, sermorelin, tesamorelin and ipamorelin act on its release. The E domain peptide from an alternative splice of the same gene is covered in MGF.
Frequently asked questions
What does DES mean in IGF-1 DES?
It is shorthand for des(1-3), the standard notation for a protein missing residues 1 through 3. In this case glycine, proline and glutamate are removed from the N-terminus of mature IGF-1, leaving 67 of the original 70 residues.
How does IGF-1 DES differ from IGF-1 LR3?
Both reduce affinity for the IGF binding proteins while keeping receptor activity, and they do it in opposite ways. DES removes the three N-terminal residues including the Glu3 that anchors binding protein contact. LR3 keeps that region but substitutes arginine at position 3 and adds a thirteen residue extension, giving an 83 residue protein of roughly 9111 g/mol. LR3 is the more stable of the two in culture.
Why does potency vary so much between published comparisons?
Because most of the difference is availability and not receptor affinity. In medium containing serum, binding proteins sequester intact IGF-1 and leave the truncated analogue free, so the measured potency gap is large. In binding-protein-free buffer the gap narrows sharply. Comparisons that do not state the binding protein content of the medium are not comparable to each other.
Is IGF-1 DES listed in the Australian Register of Therapeutic Goods?
No. IGF-1 DES is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. Recombinant material of this kind is supplied in Australia as a laboratory reagent for in vitro research.
Research use only. The compound described on this page is discussed as a laboratory chemical used in in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
