Hemopressin

Hemopressin
Names
IUPAC name
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-3-methyl-2-[[(2S)-pyrrolidine-2-carbonyl]amino]butanoyl]amino]-4-oxo-butanoyl]amino]-3-phenyl-propanoyl]amino]hexanoyl]amino]-3-phenyl-propanoyl]amino]-4-methyl-pentanoyl]amino]-3-hydroxy-propanoyl]amino]-3-(1H-imidazol-5-yl)propanoic acid
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
  • InChI=1S/C53H77N13O12/c1-30(2)22-37(47(71)65-42(28-67)51(75)64-41(53(77)78)25-34-27-56-29-58-34)60-49(73)39(24-33-16-9-6-10-17-33)61-46(70)36(18-11-12-20-54)59-48(72)38(23-32-14-7-5-8-15-32)62-50(74)40(26-43(55)68)63-52(76)44(31(3)4)66-45(69)35-19-13-21-57-35/h5-10,14-17,27,29-31,35-42,44,57,67H,11-13,18-26,28,54H2,1-4H3,(H2,55,68)(H,56,58)(H,59,72)(H,60,73)(H,61,70)(H,62,74)(H,63,76)(H,64,75)(H,65,71)(H,66,69)(H,77,78)/t35-,36-,37-,38-,39-,40-,41-,42-,44-/m0/s1 ☒N
    Key: DUTLYPZZJJBEAJ-QISMNGAHSA-N ☒N
  • InChI=1/C53H77N13O12/c1-30(2)22-37(47(71)65-42(28-67)51(75)64-41(53(77)78)25-34-27-56-29-58-34)60-49(73)39(24-33-16-9-6-10-17-33)61-46(70)36(18-11-12-20-54)59-48(72)38(23-32-14-7-5-8-15-32)62-50(74)40(26-43(55)68)63-52(76)44(31(3)4)66-45(69)35-19-13-21-57-35/h5-10,14-17,27,29-31,35-42,44,57,67H,11-13,18-26,28,54H2,1-4H3,(H2,55,68)(H,56,58)(H,59,72)(H,60,73)(H,61,70)(H,62,74)(H,63,76)(H,64,75)(H,65,71)(H,66,69)(H,77,78)/t35-,36-,37-,38-,39-,40-,41-,42-,44-/m0/s1
    Key: DUTLYPZZJJBEAJ-QISMNGAHBC
  • CC(C)C[C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1cnc[nH]1)C(=O)O)NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](Cc3ccccc3)NC(=O)[C@H](CC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]4CCCN4
Properties
C53H77N13O12
Molar mass 1088.25838
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Hemopressin (Hp) is an alpha hemoglobin fragment with the sequence PVNFKFLSH, originally identified in extracts of rat brain using an enzyme capture technique.[1] It binds cannabinoid receptors, acting as an inverse agonist at CB1 receptors.[2] Longer forms of hemopressin containing 2-3 additional amino acids on the N-terminus have been identified in extracts of mouse brain. These longer hemopressin peptides, named RVD-Hpα and VD-Hpα, bind to CB1 receptors and were originally reported to be agonists.[3] In addition to the Hp peptides from alpha hemoglobin, a related peptide from beta hemoglobin has been found in mouse brain extracts; this peptide, named VD-Hpβ, is also an agonist at CB1 cannabinoid receptors.[3] Hemopressin is not an endogenous peptide but rather an extraction artefact.[4] The only endogenous peptide found endogenously at physiological conditions is RVD-hemopressin (pepcan-12), which has more recently been shown to be a negative allosteric modulator of CB1 receptors and positive allosteric modulator of CB2 receptors.[4][5] RVD-hemopressin (pepcan-12) is generated from a pro-peptide called pepcan-23 and these peptides are exclusively found in noradrenergic neurons in the brain and in the adrenal medulla.[6]

The original Hp peptide reduces sensitivity to painful stimuli in an experimental model of hyperalgesia.[7] Hp also reduces food intake in mice.[8] However, it remains to be shown if Hp is an endogenous brain peptide. The original purification used boiling acid to extract the peptide from rat brain, and hot acid can specifically cleave D-P bonds. The N-terminally-extended forms RVD-Hpα and VD-Hpα may represent the true endogenous forms.[9]

  1. ^ Rioli V, Gozzo FC, Heimann AS, et al. (March 2003). "Novel natural peptide substrates for endopeptidase 24.15, neurolysin, and angiotensin-converting enzyme". J. Biol. Chem. 278 (10): 8547–55. doi:10.1074/jbc.M212030200. PMID 12500972.
  2. ^ Heimann AS, Gomes I, Dale CS, et al. (December 2007). "Hemopressin is an inverse agonist of CB1 cannabinoid receptors". Proc. Natl. Acad. Sci. U.S.A. 104 (51): 20588–93. Bibcode:2007PNAS..10420588H. doi:10.1073/pnas.0706980105. PMC 2154475. PMID 18077343.
  3. ^ a b Gomes I, Grushko JS, Golebiewska U, et al. (September 2009). "Novel endogenous peptide agonists of cannabinoid receptors". FASEB J. 23 (9): 3020–9. doi:10.1096/fj.09-132142. PMC 2735371. PMID 19380512.
  4. ^ a b Bauer, Mark; Chicca, Andrea; Tamborrini, Marco; Eisen, David; Lerner, Raissa; Lutz, Beat; Poetz, Oliver; Pluschke, Gerd; Gertsch, Jürg (2012). "Identification and Quantification of a New Family of Peptide Endocannabinoids (Pepcans) Showing Negative Allosteric Modulation at CB1 Receptors". Journal of Biological Chemistry. 287 (44). Elsevier BV: 36944–36967. doi:10.1074/jbc.m112.382481. ISSN 0021-9258. PMC 3481297. PMID 22952224.
  5. ^ Petrucci, Vanessa; Chicca, Andrea; Glasmacher, Sandra; Paloczi, Janos; Cao, Zongxian; Pacher, Pal; Gertsch, Jürg (2017-08-25). "Pepcan-12 (RVD-hemopressin) is a CB2 receptor positive allosteric modulator constitutively secreted by adrenals and in liver upon tissue damage". Scientific Reports. 7 (1). Springer Science and Business Media LLC: 9560. Bibcode:2017NatSR...7.9560P. doi:10.1038/s41598-017-09808-8. ISSN 2045-2322. PMC 5573408. PMID 28842619.
  6. ^ Hofer, Stefanie C.; Ralvenius, William T.; Gachet, M. Salomé; Fritschy, Jean-Marc; Zeilhofer, Hanns Ulrich; Gertsch, Jürg (2015). "Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla". Neuropharmacology. 98. Elsevier BV: 78–89. doi:10.1016/j.neuropharm.2015.03.021. ISSN 0028-3908. PMID 25839900. S2CID 43599023.
  7. ^ Dale CS, Pagano Rde L, Rioli V, et al. (March 2005). "Antinociceptive action of hemopressin in experimental hyperalgesia". Peptides. 26 (3): 431–6. doi:10.1016/j.peptides.2004.10.026. PMID 15652650. S2CID 1402750.
  8. ^ Dodd GT, Mancini G, Lutz B, et al. (May 2010). "The peptide hemopressin acts through CB1 cannabinoid receptors to reduce food intake in rats and mice". J. Neurosci. 30 (21): 7369–76. doi:10.1523/JNEUROSCI.5455-09.2010. PMC 6632410. PMID 20505104.
  9. ^ Gelman JS, Sironi J, Castro LM, et al. (May 2010). "Hemopressins and other hemoglobin-derived peptides in mouse brain: comparison between brain, blood, and heart peptidome and regulation in Cpefat/fat mice". J. Neurochem. 113 (4): 871–80. doi:10.1111/j.1471-4159.2010.06653.x. PMC 2867603. PMID 20202081.