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DeutschModified GRF (1-29)
| Modified GRF (1-29) | |
|---|---|
| Identifiers | |
| Symbol | Mod GRF (1-29) |
Modified GRF (1-29) often abbreviated as mod GRF (1-29), originally known as tetrasubstituted GRF (1-29), is a term used to identify a 29 amino acid peptide analogue of growth-hormone-releasing hormone (GHRH), a releasing hormone of growth hormone (GH). It is a modified version of the shortest fully functional fragment of GHRH, often referred to as growth hormone releasing factor (1-29) (abbreviated as GRF (1-29)), and also known by its standardized name, sermorelin.
Origin
[edit]The first 29 amino acids of GHRH were discovered to be as equally potent as its full 44 amino acid structure[1][2] This fragment became known as GRF (1-29). However, due to a rapid metabolic clearance analogues of GRF (1-29) were synthesized to enhance the biological activity and reduce the rapidity of metabolic clearance. These analogues were primarily created by substituting amino acids within the peptide structure for amino acids more resistant to enzymatic cleavage. One early analogue substituted the amino acid L-alanine (abbreviated as Ala or A) at the 2nd position of the peptide structure for its optical isomer (mirror image), D-alanine (abbreviated as D-Ala). This substitution resulted in a peptide bond between D-Ala and the 3rd amino acid in the structure aspartic acid (Asp) more able to resist rapid cleavage by the enzyme dipeptidyl peptidase-4, a cleavage which had previously led to an inactive peptide fragment.[3][4] This successful modification prompted the further creation of analogues with additional amino acid substitutions.
In 2005, the first specific mention of tetrasubstituted GRF (1-29) appeared in a study that used it as one of the GRF (1-29) analogue peptide structures studied.[5] The term was used to describe the replacement of the 2nd, 8th, 15th, and 27th amino acids in the structure of GRF (1-29).
In 2008, a researcher known as DatBtrue created the term modified GRF (1-29) in place of tetrasubstitued GRF (1-29) in his public articles. Continued use of the term on public and private forums has popularized and standardized the nomenclature.[citation needed]
Effect
[edit]Modified GRF (1-29) acts to increase growth hormone production and release by binding to the growth-hormone-releasing hormone receptor (GHRHR) on cells in the anterior pituitary.
Structure
[edit]GRF (1-29), also known as sermorelin (Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2), the biologically-active portion of the 44 amino acid GHRH. Half-life "less than 10 minutes", perhaps as low as 5 minutes.[6]
Mod GRF (1-29) replacement of the 2nd, 8th, 15th, and 27th amino acids of GRF (1-29) yields modified GRF(1-29) (Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-NH2). Half-life at least 30 minutes.[7][8]
See also
[edit]References
[edit]- ^ Wehrenberg WB, Ling N (1983). "In vivo biological potency of rat and human growth hormone-releasing factor and fragments of human growth hormone-releasing factor". Biochem Biophys Res Commun. 115 (2): 525–530. doi:10.1016/S0006-291X(83)80176-4. PMID 6414471.
- ^ Grossman A, Savage MO, Lytras N, et al. (1984). "Responses to analogues of growth hormone-releasing hormone in normal subjects, and in growth-hormone deficient children and young adults". Clin Endocrinol. 21 (3): 321–330. doi:10.1111/j.1365-2265.1984.tb03477.x. PMID 6236914.
- ^ Scarborough R, Gulyas J, Schally AV, Reeves JJ (1988). "Analogs of growth hormone-releasing hormone induce release of growth hormone in the bovine". J Anim Sci. 66 (6): 1386–1392. doi:10.2527/jas1988.6661386x. PMID 3135287.
- ^ Soule S, King JA, Millar RP (1994). "Incorporation of D-Ala2 in growth hormone-releasing hormone-(1-29)-NH2 increases the half-life and decreases metabolic clearance in normal men". J Clin Endocrinol Metab. 79 (4): 1208–1211. doi:10.1210/jcem.79.4.7962295. PMID 7962295.
- ^ Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP (2005). "Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog". Endocrinology. 146 (7): 3052–8. doi:10.1210/en.2004-1286. PMID 15817669.
- ^ Frohman LA (1986). "Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH2 terminus". J Clin Invest. 78 (4): 906–913. doi:10.1172/JCI112679. PMC 423714. PMID 3093533.
- ^ Izdebski J (2002). "New potent hGH-RH analogues with increased resistance to enzymatic degradation". JJ Pept Sci. 8 (7): 285–287. doi:10.1002/psc.409. PMID 12148777.
- ^ Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP (2005). "Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats: Identification of CJC-1295 as a Long-Lasting GRF Analog". Endocrinology. 146 (7): 3052–8. doi:10.1210/en.2004-1286. PMID 15817669.