IGF-1 DES Research: The des(1-3) Truncation and the Binding-Protein Story

What is IGF-1 DES?

What is IGF-1 DES? It is human insulin-like growth factor 1 missing its first three N-terminal residues — glycine, proline and glutamate — and the literature name for it is des(1–3)IGF-I. Mature IGF-1 is a 70-residue single-chain polypeptide (UniProt P05019, residues 49–118 of the 195-residue precursor); the truncated form is 67 residues, retaining the same three intrachain disulfide bonds and the same receptor-binding architecture.

One thing distinguishes it from most compounds in the sourcing catalogue: it is not an invented analogue. Des(1–3)IGF-I occurs naturally. It was purified from bovine colostrum (Francis et al. 1988, Biochem J, PMID 3390164), identified in brain tissue, and Yamamoto & Murphy (1995, J Endocrinol, PMID 7561610) reported that rat serum and tissues enzymatically convert IGF-I to des(1–3)IGF-I. Ballard and colleagues (1996, Int J Biochem Cell Biol, PMID 8930132) devoted a short dedicated review to it. Molecular description only; nothing here describes an effect in a reader.

Discovery and origin in the literature

The compound entered the record through a purification puzzle. Work on IGF-1 from bovine colostrum in the mid-1980s kept turning up a form that was more potent than the intact molecule in cell assays. Francis et al. (1988) sequenced the colostrum growth factors and compared their biological activities with those of “a potent truncated form” — the phrase in the paper’s own title. Ballard, Francis, Ross and colleagues (1987, Biochem Biophys Res Commun, PMID 2962574) had already set out the explanation: destripeptide IGF-1 bound the IGF-1 receptor comparably to the intact molecule while showing much weaker interaction with the binding proteins, and the potency difference tracked the binding-protein difference rather than the receptor one.

Carlsson-Skwirut et al. (1989, Biochim Biophys Acta, PMID 2469478) compared recombinant intact and truncated IGF-1 side by side and reached a consistent conclusion. A companion strand of that group’s work went in an unexpected direction: Sara et al. (1989, Biochem Biophys Res Commun, PMID 2574573) identified the removed tripeptide itself — Gly-Pro-Glu, GPE — as a neuroactive peptide in its own right, which is worth knowing because it means the truncation reaction produces two biologically studied molecules, not one plus a discarded fragment.

By the early 1990s the field had generalised the lesson. Francis et al. (1992, J Mol Endocrinol, PMID 1378742) compared a series of engineered analogues designed to disrupt IGFBP contact — the paper that also introduced the Long [Arg3] form now sold as IGF-1 LR3 — and concluded that binding-protein escape, not receptor affinity, was what drove the enhanced potency of the whole series.

Reference data

Sequence and residue boundaries are taken from the UniProt human IGF-1 record (P05019); the mass below is calculated from that sequence with residues 1–3 of the mature chain removed. No CAS number could be sourced for the truncated form, so that field is omitted rather than guessed.

Molecule and analytical facts only. No reconstitution volume, concentration, route or handling instruction is given or implied.

Mechanisms researchers have examined

The IGF-1 DES mechanism is unusually easy to state because the molecule was defined by one variable:

• Loss of IGFBP affinity — the N-terminal tripeptide contributes to the surface that IGF-binding proteins recognise. Removing it leaves the truncated peptide far less able to be sequestered by the six IGFBPs that normally carry and buffer IGF-1 in circulation and in culture medium (Ballard et al. 1987; Ballard et al. 1996).
• Preserved IGF-1 receptor engagement — the receptor-binding face of the molecule is not the face that was cut. Receptor affinity is reported as broadly retained, which is why the truncation changes availability rather than signalling identity.
• The consequence for measured potency — in any system containing IGFBPs, more of the administered material remains free, so apparent potency rises. Francis et al. (1992) made this explicit across an analogue series: the ranking of potency followed the ranking of binding-protein escape.
• Faster clearance as the other side of the same coin — IGFBPs prolong the residence of IGF-1 in circulation. A molecule that escapes them also loses that reservoir. Gillespie et al. (1996, Am J Physiol, PMID 8897852) measured plasma clearance of IGF-I, des(1–3)IGF-I and LR3 IGF-I directly, including in chronic renal failure — a rare head-to-head of the three molecules on a pharmacokinetic endpoint.
• Downstream signalling — the pathways studied are those of the IGF-1 receptor generally (PI3K/Akt, Ras/MAPK-ERK). Nothing in this literature proposes a signalling pathway unique to the truncated form.

Research findings by area

Comparative anabolic work in rodents

Tomas and colleagues (1992, Biochem J, PMID 1371669) compared IGF-I with IGF-I variants in dexamethasone-treated rats, a catabolic model, and reported that the variants were anabolic in that setting — the paper’s title states “and especially IGF-I variants”. Related work from the same programme (Read et al. 1992) examined gut growth in the same model. These are rodent studies in a pharmacologically induced catabolic state, and they measured tissue and body-weight endpoints in animals; they are reported here as what the studies measured.

The finding that is usually left out: glucose

Tomas et al. (1997, J Endocrinol, PMID 9415072) tested IGF-I variants that bind poorly to IGFBPs in pigs and marmoset monkeys and reported that they showed more potent and more prolonged hypoglycaemic action than native IGF-I. This is the direct pharmacological consequence of removing the buffering system: IGF-1 has insulin-like activity, IGFBPs restrain it, and an analogue that escapes them expresses more of it. It is a documented animal finding, it appears in the title of a peer-reviewed paper, and it is the observation most conspicuously absent from vendor descriptions of this compound. This page reports it because it is what the literature says, not as advice of any kind.

Cell-system work

Beyond the founding comparisons, des(1–3)IGF-I appears through the 1990s as a tool compound in cell and organ-culture studies precisely because it sidesteps IGFBPs secreted into the medium — the same logical role that LR3 IGF-I occupies in serum-free bioprocess work. Carlsson-Skwirut et al. (1989) is the reference comparison for intact versus truncated activity in that setting.

Research models and evidence status

The models are biochemical, in vitro and animal: cell assays, rodents, pigs and marmoset monkeys, plus analytical method development in anti-doping laboratories. The mechanistic account is well supported and, unusually for this catalogue, essentially uncontested — the binding-protein explanation was proposed in 1987 and has held.

What is not established

No interventional human trial of des(1–3)IGF-I has been published. No approved product contains it and it holds no registered indication anywhere. The animal work measured potency, clearance and tissue endpoints in specific experimental models — a dexamethasone-induced catabolic state, chronic renal failure, growth-hormone-manipulated animals — and those findings cannot be extended to healthy humans. The 1997 pig and marmoset study reported enhanced and prolonged hypoglycaemic action for poor-IGFBP-binding variants, and no work has established what that would mean in people. No long-term safety data exist. Nothing above is a benefit, an outcome or a use.

On anti-doping status, reported as fact and not as a use case: IGF-1 and its analogues fall under section S2 of the World Anti-Doping Agency Prohibited List and are prohibited at all times. Mongongu et al. (2021, Drug Test Anal, PMID 33587816) developed and published an immunopurification plus high-resolution mass spectrometry method that detects and distinguishes LongR3-IGF-I, des(1–3)-IGF-I and R3-IGF-I — which is also the clearest published demonstration that the three are analytically separable molecules.

IGF-1 DES versus IGF-1 LR3, and the rest of the cluster

These two are the pair most often conflated, and the difference is structural. DES is a deletion: 67 residues, three taken off the front, roughly 7.37 kDa. LR3 is an addition plus a substitution: 83 residues, a 13-residue N-terminal extension and an arginine at position 3, roughly 9.1 kDa. Both reduce IGFBP affinity and both preserve receptor binding; Francis et al. (1992) characterised them within the same analogue series, and Gillespie et al. (1996) measured both alongside native IGF-I. Their downstream biology is the shared IGF-1 receptor story. The IGF-1 LR3 page covers that analogue and its documented role as a serum-free culture supplement; this page does not restate it.

Further out sit the other members of this cluster, and the direction of action is what separates them. MGF and PEG-MGF are E-domain fragments of the same gene product with no identified receptor. In the opposite direction, GDF-8 is myostatin — a negative regulator and a target, not an agonist; follistatin-344 is an endogenous antagonist of it; and ACE-031 is a soluble receptor decoy whose clinical programme was stopped on safety grounds. Mechanism context only; nothing here is a protocol, a stack or a recommendation.

How to verify this compound yourself

Identity is the check that matters most on this molecule, because its nearest relatives differ from it in ways no purity figure can reveal:

• Mass-spec identity — native IGF-1, des(1–3)IGF-I and LR3 IGF-I have clearly different masses (roughly 7.65, 7.37 and 9.1 kDa), so a mass measurement separates them unambiguously. Mongongu et al. (2021) built exactly this discrimination into a validated anti-doping method. A vial of native IGF-1 sold as DES would be a pure, correct, entirely different product, and only a mass spectrum would show it.
• HPLC purity — reversed-phase chromatography reports purity as a percentage of the chromatogram and resolves synthesis- or expression-related impurities. For a recombinant protein of this size, purity methods are often paired with SDS-PAGE.
• Correct disulfide folding — a 67-residue chain with three disulfide bonds can be the right sequence and the wrong molecule if it is misfolded. Mass alone will not distinguish reduced from oxidised species reliably; chromatographic behaviour and, where reported, bioassay data speak to it.
• Endotoxin and sterility — where tested, separate quality attributes reported in EU/mg or as a sterility result, independent of chemical purity.

See how to read a COA for what each line on a certificate means, how to verify peptide purity for how the methods fit together, and the self-serve verify tool to check the exact batch on a vial in hand.

Research-grade sourcing and verification

For laboratory research use only. IGF-1 DES is not held in stock; it is listed as available to order in the sourcing catalogue, with a typical lead time of two to three weeks and a quote on request. Material supplied ships with a per-batch Certificate of Analysis reporting purity and mass-spec identity confirmation at the lot level — the check that separates a 67-residue truncation from a 70-residue native protein and an 83-residue analogue. Sourcing and identity-assurance framing only.

Frequently asked questions

Literature cited

1. Ballard FJ, Francis GL, Ross M, Bagley CJ, May B, Wallace JC. “Natural and synthetic forms of insulin-like growth factor-1 (IGF-1) and the potent derivative, destripeptide IGF-1: biological activities and receptor binding.” Biochem Biophys Res Commun. 1987;149(2):398–404. PMID 2962574. pubmed.ncbi.nlm.nih.gov/2962574.
2. Francis GL, Upton FM, Ballard FJ, McNeil KA, Wallace JC. “Insulin-like growth factors 1 and 2 in bovine colostrum. Sequences and biological activities compared with those of a potent truncated form.” Biochem J. 1988;251(1):95–103. PMID 3390164. pubmed.ncbi.nlm.nih.gov/3390164.
3. Carlsson-Skwirut C, Lake M, Hartmanis M, Hall K, Sara VR. “A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1).” Biochim Biophys Acta. 1989;1011(2-3):192–7. PMID 2469478. pubmed.ncbi.nlm.nih.gov/2469478.
4. Sara VR, Carlsson-Skwirut C, Bergman T, et al. “Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide.” Biochem Biophys Res Commun. 1989;165(2):766–71. PMID 2574573. pubmed.ncbi.nlm.nih.gov/2574573.
5. Yamamoto H, Murphy LJ. “Enzymatic conversion of IGF-I to des(1-3)IGF-I in rat serum and tissues: a further potential site of growth hormone regulation of IGF-I action.” J Endocrinol. 1995;146(1):141–8. PMID 7561610. pubmed.ncbi.nlm.nih.gov/7561610.
6. Ballard FJ, Wallace JC, Francis GL, Read LC, Tomas FM. “Des(1-3)IGF-I: a truncated form of insulin-like growth factor-I.” Int J Biochem Cell Biol. 1996;28(10):1085–7. PMID 8930132. pubmed.ncbi.nlm.nih.gov/8930132.
7. 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.” J Mol Endocrinol. 1992;8(3):213–23. PMID 1378742. pubmed.ncbi.nlm.nih.gov/1378742.
8. Tomas FM, Knowles SE, Owens PC, et al. “Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats.” Biochem J. 1992;282(Pt 1):91–7. PMID 1371669. pubmed.ncbi.nlm.nih.gov/1371669.
9. Read LC, Tomas FM, Howarth GS, et al. “Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats.” J Endocrinol. 1992;133(3):421–31. PMID 1613443. pubmed.ncbi.nlm.nih.gov/1613443.
10. Tomas FM, Lemmey AB, Read LC, Ballard FJ. “IGF-I variants which bind poorly to IGF-binding proteins show more potent and prolonged hypoglycaemic action than native IGF-I in pigs and marmoset monkeys.” J Endocrinol. 1997;155(2):377–86. PMID 9415072. pubmed.ncbi.nlm.nih.gov/9415072.
11. Gillespie CM, Merkel AL, Martin AA. “Effects of chronic renal failure on plasma clearance of insulin-like growth factor I, des-(1-3)IGF-I, and LR3IGF-I.” Am J Physiol. 1996;271(4 Pt 1):E649–57. PMID 8897852. pubmed.ncbi.nlm.nih.gov/8897852.
12. Mongongu C, Coudoré F, Marchand A, et al. “Detection of LongR3-IGF-I, Des(1-3)-IGF-I, and R3-IGF-I using immunopurification and high resolution mass spectrometry for antidoping purposes.” Drug Test Anal. 2021;13(7):1256–1269. PMID 33587816. pubmed.ncbi.nlm.nih.gov/33587816.
13. UniProt Consortium. “IGF1_HUMAN (P05019) — Insulin-like growth factor 1.” uniprot.org/uniprotkb/P05019 (precursor length, mature chain boundaries, sequence).