Mechano growth factor

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Mechano growth factor
MGF structure.png
Identifiers
  • (2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S,3R)-2-[[(2S)-4-amino-2-[[(2S)-6-amino-2-[[(2S)-4-amino-2-[[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S)-1-[(2S)-5-amino-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-4-oxobutanoyl]amino]hexanoyl]amino]-4-oxobutanoyl]amino]-3-hydroxybutanoyl]amino]hexanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoyl]amino]acetyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxybutanoyl]amino]-4-carboxybutanoyl]amino]-5-carbamimidamidopentanoyl]amino]hexanoic acid
PubChem CID
Chemical and physical data
Formula C121H199N41O40
Molar mass 2868.170 g·mol−1
3D model (JSmol)
  • C[C@H]([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]3CCCN3C(=O)[C@H](CCC(=O)N)NC(=O)[C@H](CC4=CC=C(C=C4)O)N)O
  • InChI=1S/C121H199N41O40/c1-60(166)93(158-108(191)80(55-89(130)173)153-101(184)68(23-8-12-44-123)146-107(190)79(54-88(129)172)155-115(198)95(62(3)168)160-111(194)83(59-165)157-112(195)84-29-18-50-161(84)117(200)85-30-19-51-162(85)116(199)76(36-40-87(128)171)151-96(179)66(126)52-64-31-33-65(169)34-32-64)113(196)150-69(24-9-13-45-124)102(185)156-82(58-164)109(192)149-73(35-39-86(127)170)103(186)144-71(27-16-48-138-120(133)134)99(182)143-70(26-15-47-137-119(131)132)98(181)142-67(22-7-11-43-122)97(180)140-56-90(174)141-81(57-163)110(193)159-94(61(2)167)114(197)154-78(53-63-20-5-4-6-21-63)106(189)148-75(38-42-92(177)178)105(188)147-74(37-41-91(175)176)104(187)145-72(28-17-49-139-121(135)136)100(183)152-77(118(201)202)25-10-14-46-125/h4-6,20-21,31-34,60-62,66-85,93-95,163-169H,7-19,22-30,35-59,122-126H2,1-3H3,(H2,127,170)(H2,128,171)(H2,129,172)(H2,130,173)(H,140,180)(H,141,174)(H,142,181)(H,143,182)(H,144,186)(H,145,187)(H,146,190)(H,147,188)(H,148,189)(H,149,192)(H,150,196)(H,151,179)(H,152,183)(H,153,184)(H,154,197)(H,155,198)(H,156,185)(H,157,195)(H,158,191)(H,159,193)(H,160,194)(H,175,176)(H,177,178)(H,201,202)(H4,131,132,137)(H4,133,134,138)(H4,135,136,139)/t60-,61-,62-,66+,67+,68+,69+,70+,71+,72+,73+,74+,75+,76+,77+,78+,79+,80+,81+,82+,83+,84+,85+,93+,94+,95+/m1/s1
  • Key:TXMSCWQMYNJNDC-XGJLPCLZSA-N

Mechano growth factor (MGF, IGF-IEc) is a naturally occurring 24-amino acid peptide which is the C-terminal fragment derived from enzymatic cleavage of insulin-like growth factor 1 (IGF-1). It is expressed during muscle repair following physical activity, and has anabolic effects. [1] [2] [3] [4] [5] [6] [7] This has led to illicit use by athletes leading to MGF being banned by the World Anti-Doping Association, [8] [9] [10] and concerns have been raised about potential tumor promoting activity. [11]

Contents

Structure and variations

The amino acid sequence is reasonably highly conserved among mammalian species, with the native human sequence being YQPPSTNKNTKSQRRKGSTFEERK or Tyr‑Gln‑Pro‑Pro‑Ser‑Thr‑Asn‑Lys‑Asn‑Thr‑Lys‑Ser‑Gln‑Arg‑Arg‑Lys‑Gly‑Ser‑Thr‑Phe‑Glu‑Glu‑Arg‑Lys. However, there are also several other splice variants of IGF-1 aside from MGF. [12] Multiple forms of MGF are used in scientific research such as the native mouse or rat form which have several amino acid changes, or a consensus sequence mainly based on the human sequence but with the arginine changed to histidine at position 23 and sometimes other substitutions, to more closely resemble the rodent version. Since mechano growth factor is rapidly metabolised in vivo, synthetic versions often use two or more unnatural D-amino acids in the central "QRRK" portion at positions 13-16, as well as sometimes at the N-terminal tyrosine, to improve metabolic stability, and the tyrosine OH can also be PEGylated. [13] [14] [15]

See also

References

  1. ↑ Goldspink G (April 1999). "Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload". Journal of Anatomy. 194 (Pt 3): 323–334. doi:10.1046/j.1469-7580.1999.19430323.x. PMC   1467932 . PMID   10386770.
  2. ↑ Goldspink G (June 2004). "Age-related loss of skeletal muscle function; impairment of gene expression". Journal of Musculoskeletal & Neuronal Interactions. 4 (2): 143–147. PMID   15615114.
  3. ↑ Wackerhage H, Ratkevicius A (2008). "Signal transduction pathways that regulate muscle growth". Essays in Biochemistry. 44: 99–108. doi:10.1042/BSE0440099. PMID   18384285.
  4. ↑ Matheny RW, Nindl BC, Adamo ML (March 2010). "Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration". Endocrinology. 151 (3): 865–875. doi:10.1210/en.2009-1217. PMC   2840678 . PMID   20130113.
  5. ↑ Zabłocka B, Goldspink PH, Goldspink G, Górecki DC (2012). "Mechano-Growth Factor: an important cog or a loose screw in the repair machinery?". Frontiers in Endocrinology. 3: 131. doi: 10.3389/fendo.2012.00131 . PMC   3485521 . PMID   23125840.
  6. ↑ Zanou N, Gailly P (November 2013). "Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways". Cellular and Molecular Life Sciences. 70 (21): 4117–4130. doi:10.1007/s00018-013-1330-4. PMC   11113627 . PMID   23552962.
  7. ↑ Sha Y, Chen L, Xu C, Zhang B, Hong H, Wang C (2023). "The Roles of IGF-1 and MGF on Nerve Regeneration under Hypoxia- Ischemia, Inflammation, Oxidative Stress, and Physical Trauma". Current Protein & Peptide Science. 24 (2): 143–155. doi:10.2174/1389203724666221208145549. PMID   36503467.
  8. ↑ Bachl N, Derman W, Engebretsen L, Goldspink G, Kinzlbauer M, Tschan H, et al. (December 2009). "Therapeutic use of growth factors in the musculoskeletal system in sports-related injuries". The Journal of Sports Medicine and Physical Fitness. 49 (4): 346–357. PMID   20087293.
  9. ↑ Thevis M, Thomas A, Geyer H, Schänzer W (December 2014). "Mass spectrometric characterization of a biotechnologically produced full-length mechano growth factor (MGF) relevant for doping controls". Growth Hormone & IGF Research. 24 (6): 276–280. doi:10.1016/j.ghir.2014.10.004. PMID   25466910.
  10. ↑ Cox HD, Miller GD, Eichner D (October 2017). "Detection and in vitro metabolism of the confiscated peptides BPC 157 and MGF R23H". Drug Testing and Analysis. 9 (10): 1490–1498. doi:10.1002/dta.2152. PMID   28035768.
  11. ↑ Kasprzak A, Szaflarski W (September 2020). "Role of Alternatively Spliced Messenger RNA (mRNA) Isoforms of the Insulin-Like Growth Factor 1 (IGF1) in Selected Human Tumors". International Journal of Molecular Sciences. 21 (19): 6995. doi: 10.3390/ijms21196995 . PMC   7582825 . PMID   32977489.
  12. ↑ Vassilakos G, Philippou A, Tsakiroglou P, Koutsilieris M (2014). "Biological activity of the e domain of the IGF-1Ec as addressed by synthetic peptides". Hormones. 13 (2): 182–196. doi:10.1007/BF03401333. PMID   24776619.
  13. ↑ Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SK, Ramesh B, et al. (November 2005). "A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia". FASEB Journal. 19 (13): 1896–1898. doi: 10.1096/fj.05-3786fje . PMID   16144956.
  14. ↑ Mavrommatis E, Shioura KM, Los T, Goldspink PH (September 2013). "The E-domain region of mechano-growth factor inhibits cellular apoptosis and preserves cardiac function during myocardial infarction". Molecular and Cellular Biochemistry. 381 (1–2): 69–83. doi:10.1007/s11010-013-1689-4. PMC   3720995 . PMID   23712705.
  15. ↑ Tang JJ, Podratz JL, Lange M, Scrable HJ, Jang MH, Windebank AJ (July 2017). "Mechano growth factor, a splice variant of IGF-1, promotes neurogenesis in the aging mouse brain". Molecular Brain. 10 (1) 23. doi: 10.1186/s13041-017-0304-0 . PMC   5501366 . PMID   28683812.
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