IGF-1 LR3

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IGF-1 LR3
Clinical data
Other namesLong R3-IGF-1;
IGF-1 Long R3
Routes of
administration 		Injection
ATC code
  • None
Pharmacokinetic data
Elimination half-life 56-72 hours
Identifiers
CAS Number
ChemSpider
  • none
UNII
Chemical and physical data
Formula C400H625N111O115S9
Molar mass 9117.60 g·mol−1

Long arginine 3-IGF-1, abbreviated as IGF-1 LR3 or LR3-IGF-1, is a synthetic protein and lengthened analogue of human insulin-like growth factor 1 (IGF-1). [1] [2] It differs from native IGF-1 in that it possesses an arginine instead of a glutamic acid at the third position in its amino acid sequence ("arginine 3"), and also has an additional 13 amino acids at its N-terminus (MFPAMPLLSLFVN) ("long"), for a total of 83 amino acids (relative to the 70 of IGF-1). [2] The consequences of these modifications are that IGF-1 LR3 retains the pharmacological activity of IGF-1 as an agonist of the IGF-1 receptor, has very low affinity for the insulin-like growth factor-binding proteins (IGFBPs), and has improved metabolic stability. [1] [2] As a result, it is approximately three times more potent than IGF-1, [3] and possesses a significantly longer half-life of about 20–30 hours (relative to IGF-1's half-life of about 12–15 hours). [4]

The amino acid sequence of IGF-1 LR3 is MFPAMPLSSL FVNGPRTLCG AELVDALQFV CGDRGFYFNK PTGYGSSSRR APQTGIVDEC CFRSCDLRRL EMYCAPLKPA KSA. [5]

See also

Related Research Articles

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The insulin-like growth factors (IGFs) are proteins with high sequence similarity to insulin. IGFs are part of a complex system that cells use to communicate with their physiologic environment. This complex system consists of two cell-surface receptors, two ligands, a family of seven high-affinity IGF-binding proteins, as well as associated IGFBP degrading enzymes, referred to collectively as proteases.

Insulin receptor Mammalian protein found in Homo sapiens

The insulin receptor (IR) is a transmembrane receptor that is activated by insulin, IGF-I, IGF-II and belongs to the large class of receptor tyrosine kinase. Metabolically, the insulin receptor plays a key role in the regulation of glucose homeostasis, a functional process that under degenerate conditions may result in a range of clinical manifestations including diabetes and cancer. Insulin signalling controls access to blood glucose in body cells. When insulin falls, especially in those with high insulin sensitivity, body cells begin only to have access to lipids that do not require transport across the membrane. So, in this way, insulin is the key regulator of fat metabolism as well. Biochemically, the insulin receptor is encoded by a single gene INSR, from which alternate splicing during transcription results in either IR-A or IR-B isoforms. Downstream post-translational events of either isoform result in the formation of a proteolytically cleaved α and β subunit, which upon combination are ultimately capable of homo or hetero-dimerisation to produce the ≈320 kDa disulfide-linked transmembrane insulin receptor.

Insulin-like growth factor 1

Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a hormone similar in molecular structure to insulin which plays an important role in childhood growth, and has anabolic effects in adults.

Insulin-like growth factor 2 A major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults."[5]

Insulin-like growth factor 2 (IGF-2) is one of three protein hormones that share structural similarity to insulin. The MeSH definition reads: "A well-characterized neutral peptide believed to be secreted by the liver and to circulate in the blood. It has growth-regulating, insulin-like and mitogenic activities. The growth factor has a major, but not absolute, dependence on somatotropin. It is believed to be a major fetal growth factor in contrast to Insulin-like growth factor 1, which is a major growth factor in adults."

Insulin-like growth factor 1 receptor

The insulin-like growth factor 1 (IGF-1) receptor is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. This receptor mediates the effects of IGF-1, which is a polypeptide protein hormone similar in molecular structure to insulin. IGF-1 plays an important role in growth and continues to have anabolic effects in adults – meaning that it can induce hypertrophy of skeletal muscle and other target tissues. Mice lacking the IGF-1 receptor die late in development, and show a dramatic reduction in body mass. This testifies to the strong growth-promoting effect of this receptor.

Insulin-like growth factor-binding protein Transport protein for insulin-like growth factor 1

The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1).

Laron syndrome

Laron syndrome (LS), also known as growth hormone insensitivity is an autosomal recessive disorder characterized by a lack of insulin-like growth factor 1 (IGF-1)(somatomedin) production in response to growth hormone (GH)(hGH)(somatotropin). It is usually caused by inherited growth hormone receptor (GHR) mutations.

Insulin-like growth factor 2 receptor

Insulin-like growth factor 2 receptor (IGF2R), also called the cation-independent mannose-6-phosphate receptor (CI-MPR) is a protein that in humans is encoded by the IGF2R gene. IGF2R is a multifunctional protein receptor that binds insulin-like growth factor 2 (IGF2) at the cell surface and mannose-6-phosphate (M6P)-tagged proteins in the trans-Golgi network.

IGFBP3

Insulin-like growth factor-binding protein 3, also known as IGFBP-3, is a protein that in humans is encoded by the IGFBP3 gene. IGFBP-3 is one of six IGF binding proteins that have highly conserved structures and bind the insulin-like growth factors IGF-1 and IGF-2 with high affinity. IGFBP-7, sometimes included in this family, shares neither the conserved structural features nor the high IGF affinity. Instead, IGFBP-7 binds IGF1R, which blocks IGF-1 and IGF-2 binding, resulting in apoptosis.

IRS2

Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.

IGFBP2

Insulin-like growth factor-binding protein 2 is a protein that in humans is encoded by the IGFBP2 gene.

IGFBP5

Insulin-like growth factor-binding protein 5 is a protein that in humans is encoded by the IGFBP5 gene. An IGFBP5 gene was recently identified as being important for adaptation to varying water salinity in fish.

IGFBP4

Insulin-like growth factor-binding protein 4 is a protein that in humans is encoded by the IGFBP4 gene.

IGFBP6

Insulin-like growth factor-binding protein 6 (IGFBP-6) is a protein that in humans is encoded by the IGFBP6 gene.

IGFBP1

Insulin-like growth factor-binding protein 1 (IBP-1) also known as placental protein 12 (PP12) is a protein that in humans is encoded by the IGFBP1 gene.

IGF2BP1

Insulin-like growth factor 2 mRNA-binding protein 1 is a protein that in humans is encoded by the IGF2BP1 gene.

IGFBP7

Insulin-like growth factor-binding protein 7 is a protein that in humans is encoded by the IGFBP7 gene. The major function of the protein is the regulation of availability of insulin-like growth factors (IGFs) in tissue as well as in modulating IGF binding to its receptors. IGFBP7 binds to IGF with high affinity. It also stimulates cell adhesion. The protein is implicated in some cancers.

IGFALS

Insulin-like growth factor binding protein, acid labile subunit, also known as IGFALS, is a protein which in humans is encoded by the IGFALS gene.

IGF2BP2

Insulin-like growth factor 2 mRNA-binding protein 2 is a protein that in humans is encoded by the IGF2BP2 gene.

des(1-3)IGF-1 is a naturally occurring, endogenous protein, as well as drug, and truncated analogue of insulin-like growth factor 1 (IGF-1). des(1-3)IGF-1 lacks the first three amino acids at the N-terminus of IGF-1. As a result of this difference, it has considerably reduced binding to the insulin-like growth factor-binding proteins (IGFBPs) and enhanced potency relative to IGF-1.

References

  1. 1 2 Tomas FM, Lemmey AB, Read LC, Ballard FJ (1996). "Superior potency of infused IGF-I analogues which bind poorly to IGF-binding proteins is maintained when administered by injection". J. Endocrinol. 150 (1): 77–84. doi:10.1677/joe.0.1500077. PMID   8708565.
  2. 1 2 3 Mohan S, Baylink DJ (2002). "IGF-binding proteins are multifunctional and act via IGF-dependent and -independent mechanisms". J. Endocrinol. 175 (1): 19–31. doi: 10.1677/joe.0.1750019 . PMID   12379487.
  3. ↑ Tomas FM, Knowles SE, Owens PC, Chandler CS, Francis GL, Read LC, Ballard FJ (1992). "Insulin-like growth factor-I (IGF-I) and especially IGF-I variants are anabolic in dexamethasone-treated rats". Biochem. J. 282 ( Pt 1): 91–7. doi:10.1042/bj2820091. PMC   1130894 . PMID   1371669.
  4. ↑ von der Thüsen JH, Borensztajn KS, Moimas S, van Heiningen S, Teeling P, van Berkel TJ, Biessen EA (2011). "IGF-1 has plaque-stabilizing effects in atherosclerosis by altering vascular smooth muscle cell phenotype". Am. J. Pathol. 178 (2): 924–34. doi:10.1016/j.ajpath.2010.10.007. PMC   3069834 . PMID   21281823.
  5. ↑ Mario Thevis (13 December 2010). Mass Spectrometry in Sports Drug Testing: Characterization of Prohibited Substances and Doping Control Analytical Assays. John Wiley & Sons. pp. 252–. ISBN   978-1-118-03514-6.
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