IGF-1 LR3, written in the primary literature as Long-[Arg3]-IGF-I or Long R3 IGF-1, is a recombinant analog of insulin-like growth factor 1 (IGF-1) carrying two specific modifications: an arginine substituted for the glutamate normally found at position 3 of the native sequence, and a 13-amino-acid extension added to the N-terminus. Researchers built this analog to answer a specific question in growth factor biology, whether IGF-1's growth-promoting activity could be studied separately from its extensive binding to the family of IGF-binding proteins (IGFBPs) that regulate native IGF-1 availability in circulation and tissue. Laboratories have used IGF-1 LR3 in cell assays and livestock animal models to probe IGF-1 receptor signaling with reduced interference from endogenous binding proteins.
| Attribute | Detail |
|---|---|
| Name | IGF-1 LR3, also written Long-[Arg3]-IGF-I or Long R3 IGF-1 |
| Class | Recombinant 91-amino-acid analog of insulin-like growth factor 1 |
| Modifications | Arg substituted for Glu at position 3; 13-amino-acid N-terminal extension |
| Parent molecule | Insulin-like growth factor 1 (IGF-1), a 70-amino-acid protein (UniProt entry for human IGF1) |
| What studies examine | IGF-binding-protein affinity, IGF-1 receptor signaling, protein and nitrogen metabolism in livestock and rodent models |
| Form supplied | Lyophilized powder, research use only |
What is the structure of IGF-1 LR3?
Native human IGF-1 is a 70-amino-acid single-chain protein with a folded structure that includes distinct binding surfaces for the IGF-1 receptor and for the IGF-binding protein family. King et al. (1992) reported production of recombinant IGF-1 and a set of potent analogs, including versions with glycine or arginine substituted for the native glutamate at position 3, generated in Escherichia coli as fusion proteins. Francis et al. (1992) extended this work with a systematic series of fusion-protein analogs designed to test how N-terminal extensions and position-3 substitutions each contributed to IGF-binding-protein affinity versus IGF-1 receptor binding, work that identified the combination now referred to as Long R3 IGF-1. Laajoki et al. (1997) later resolved the secondary structure of the labeled peptide by multidimensional NMR spectroscopy, confirming that the added N-terminal residues and the substitution did not disrupt the core folded structure responsible for receptor engagement.
Why does IGF-1 LR3 have reduced affinity for IGF-binding proteins?
In circulation and in tissue, native IGF-1 is bound by a family of six IGF-binding proteins that regulate its availability to the IGF-1 receptor and extend its half-life. The N-terminal extension and the Arg3 substitution in IGF-1 LR3 are both located in a region of the folded protein involved in IGFBP contact, and the analog work by Francis et al. (1992) reported markedly reduced affinity for this binding-protein family compared with native IGF-1, while IGF-1 receptor binding was comparatively well preserved. This separation is the specific property that makes IGF-1 LR3 useful in research settings where investigators want to study IGF-1 receptor signaling without the confound of endogenous binding-protein sequestration.
What have animal studies examined?
Because IGF-1 LR3's defining property is reduced IGFBP affinity, several animal studies have used it to probe how IGF-1 signaling behaves when that regulatory layer is minimized. Dunaiski et al. (1997) examined Long R3 IGF-1 in pigs, reporting that it reduced growth rate, circulating growth hormone, IGFBP-3 and endogenous IGF-1 concentrations relative to controls, a finding the authors interpreted as evidence of feedback suppression of the growth-hormone axis in that model. Hill et al. (1999) studied its effects on protein metabolism in beef heifers, tracking nitrogen balance and whole-body protein turnover. Tomas et al. (1991) had earlier examined a related truncated IGF-1 variant, des(1-3)IGF-I, in diabetic rats, reporting increased weight gain, nitrogen retention and muscle protein synthesis relative to native IGF-1 at comparable receptor engagement, work that helped motivate the later N-terminal-extension design used in Long R3 IGF-1.
How does IGF-1 LR3 differ from native IGF-1 mechanistically?
Native IGF-1 and IGF-1 LR3 are reported to engage the IGF-1 receptor with broadly comparable affinity in the cited structural and cell studies, so the functional distinction researchers describe is not a different receptor pharmacology but a different availability profile. Because native IGF-1 is largely sequestered by IGFBPs in circulation, only a small fraction is available to interact with the receptor at any given time; IGF-1 LR3's reduced IGFBP affinity means a larger proportion of the administered protein remains available to engage the receptor in the models studied. Researchers treat this as a pharmacokinetic and availability difference rather than a difference in the underlying receptor biology, and it is the reason IGF-1 LR3 shows up specifically in study designs where investigators want to minimize the buffering effect that endogenous binding proteins normally have on IGF-1 signaling in a tissue or cell system.
How is IGF-1 LR3 identified and characterized in the lab?
Because IGF-1 LR3 is a 91-amino-acid recombinant protein rather than a short synthetic peptide, confirming its identity and integrity relies on the same analytical methods used for other recombinant proteins and larger peptides in a research setting. Mass spectrometry is the standard method for confirming molecular identity, covered in more general terms in mass spectrometry for peptide identity, and net peptide content measurement, discussed in net peptide content vs purity, is relevant background for interpreting a certificate of analysis for a protein of this size.
Frequently asked questions
Is IGF-1 LR3 the same molecule as native IGF-1?
No. IGF-1 LR3 is a recombinant analog carrying an arginine substitution at position 3 and a 13-amino-acid N-terminal extension not present in native 70-amino-acid IGF-1, engineered specifically to reduce IGF-binding-protein affinity.
Why does the N-terminal extension matter?
Structural and biochemical studies place the added residues in a region involved in IGF-binding-protein contact. Francis et al. (1992) reported that this extension, combined with the Arg3 substitution, substantially reduces binding-protein affinity while largely preserving IGF-1 receptor binding.
Does IGF-1 LR3 bind the IGF-1 receptor differently than native IGF-1?
The cited structural work reports comparable receptor engagement between the two; the documented difference is in IGF-binding-protein affinity, not IGF-1 receptor pharmacology.
What animal models have been used to study IGF-1 LR3?
Published studies include pigs (Dunaiski et al., 1997) and beef heifers (Hill et al., 1999) examining growth-axis feedback and protein metabolism, building on earlier rat studies of a related truncated analog, des(1-3)IGF-I (Tomas et al., 1991).
How is IGF-1 LR3 supplied for laboratory use?
As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis. See our IGF-1 LR3 lot page for current specifications.
References
- 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):213-223. PubMed 1378742.
- King R, Wells JR, Krieg P, et al. Production and characterization of recombinant insulin-like growth factor-I (IGF-I) and potent analogues of IGF-I, with Gly or Arg substituted for Glu3, following their expression in Escherichia coli as fusion proteins. J Mol Endocrinol. 1992;8(1):29-41. PubMed 1311930.
- Laajoki LG, Le Breton E, Shooter GK, et al. Secondary structure determination of 15N-labelled human Long-[Arg-3]-insulin-like growth factor 1 by multidimensional NMR spectroscopy. FEBS Lett. 1997;420(1):97-102. PubMed 9450557.
- Dunaiski V, Dunshea FR, Walton PE, et al. Long [R3] insulin-like growth factor-I reduces growth, plasma growth hormone, IGF binding protein-3 and endogenous IGF-I concentrations in pigs. J Endocrinol. 1997;155(3):559-565. PubMed 9488001.
- Hill RA, Hunter RA, Lindsay DB, et al. Action of long(R3)-insulin-like growth factor-1 on protein metabolism in beef heifers. Domest Anim Endocrinol. 1999;16(4):219-229. PubMed 10370861.
- Tomas FM, Knowles SE, Owens PC, et al. Increased weight gain, nitrogen retention and muscle protein synthesis following treatment of diabetic rats with insulin-like growth factor (IGF)-I and des(1-3)IGF-I. Biochem J. 1991;276(Pt 2):547-554. PubMed 1710892.
- UniProt Consortium. IGF1 - Insulin-like growth factor I - Homo sapiens (human), entry P05019. UniProt P05019.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
