IGF-1 LR3

IGF-1 LR3 is an eighty-three-residue analogue of human insulin-like growth factor I carrying two deliberate changes. They are a thirteen-residue N-terminal extension, and arginine in place of glutamate at position 3 of the growth-factor chain.

Both modifications are documented in the paper that introduced the construct, Francis and colleagues in the Journal of Molecular Endocrinology in 1992, which defines it as methionyl porcine growth hormone residues 1 to 11 followed by valine and asparagine, joined to the substituted growth factor. The extension reads MFPAMPLSSLFVN. FDA GSRS registers the same thing under UNII M9L22Y19H9 and its systematic name encodes it independently.

The substitution is described in insulin-like-growth-factor numbering, and that is a numbering trap worth stating: the arginine sits at position 3 of the seventy-residue growth-factor chain, which is position 16 of the eighty-three-residue molecule actually supplied. Residues 14 to 83 are otherwise identical to the mature growth factor as annotated on UniProt P05019.

Three disulfides fix the fold, connecting residues 19 to 61, 31 to 74, and 60 to 65 in the numbering of this chain; the bonds were originally located by mass spectrometry by Raschdorf and colleagues in 1988. Francis and colleagues report that the hydrophobic extension makes correct oxidative folding easier than in the unextended protein, which is a manufacturing property rather than a property of the folded molecule.

No molecular weight or molecular formula is printed on this page, and the reason is specific. FDA GSRS publishes both but flags each as an estimate, and its protein estimator is measurably high: it returns a figure for the native growth factor about three daltons above the accepted value. The two numbers circulating in the trade, near 9111 and near 9118, are not two candidate masses but the same molecule fully oxidised and fully reduced. Until a figure with a stated oxidation state comes from a measurement rather than an estimator, printing one here would put a number next to a structure that disagrees with it.

This is routinely confused with two neighbouring molecules and is neither. Native insulin-like growth factor I, registered as mecasermin, is seventy residues with glutamate at position 3 and no extension. IGF-1 DES, CAS 112603-35-7, is sixty-seven residues: the native chain with its first three residues removed. One is an extension plus a substitution, the other is a truncation; they share no mass, formula, CAS number or residue count.

The molecule has no tryptophan, three tyrosines and six phenylalanines, so absorbance at 280 nm is usable but weak. Three methionines and six cysteines, all of the latter in disulfides, are the oxidation-relevant residues. Its receptor is IGF1R (UniProt P08069); Francis and colleagues also report cross-reaction with the insulin receptor (UniProt P06213) at high concentration in a hepatoma assay, and reduced association with insulin-like-growth-factor binding proteins, which is the stated basis for the construct's behaviour in cell lines that secrete them.