Opiorphin

Opiorphin[1]
Names
IUPAC name
(2S,5S,8S,11S,14S)-14,17-diamino-8-benzyl-2,11-bis(3-guanidinopropyl)-5-(hydroxymethyl)-4,7,10,13,17-pentaoxo-3,6,9,12-tetraazaheptadecan-1-oic acid
Other names
Gln-Arg-Phe-Ser-Arg; L-Glutaminyl-L-arginyl-L-phenylalanyl-L-seryl-L-arginine
Identifiers
CAS Number
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
InChI
  • InChI=1S/C29H48N12O8/c30-17(10-11-22(31)43)23(44)38-18(8-4-12-36-28(32)33)24(45)40-20(14-16-6-2-1-3-7-16)25(46)41-21(15-42)26(47)39-19(27(48)49)9-5-13-37-29(34)35/h1-3,6-7,17-21,42H,4-5,8-15,30H2,(H2,31,43)(H,38,44)(H,39,47)(H,40,45)(H,41,46)(H,48,49)(H4,32,33,36)(H4,34,35,37)/t17-,18-,19-,20-,21-/m0/s1 ☒N
    Key: TWWFCOBVAKAKIT-SXYSDOLCSA-N ☒N
  • InChI=1/C29H48N12O8/c30-17(10-11-22(31)43)23(44)38-18(8-4-12-36-28(32)33)24(45)40-20(14-16-6-2-1-3-7-16)25(46)41-21(15-42)26(47)39-19(27(48)49)9-5-13-37-29(34)35/h1-3,6-7,17-21,42H,4-5,8-15,30H2,(H2,31,43)(H,38,44)(H,39,47)(H,40,45)(H,41,46)(H,48,49)(H4,32,33,36)(H4,34,35,37)/t17-,18-,19-,20-,21-/m0/s1
    Key: TWWFCOBVAKAKIT-SXYSDOLCBM
SMILES
  • O=C([C@H](CO)NC([C@H](CC1=CC=CC=C1)NC([C@H](CCCNC(N)=N)NC([C@H](CCC(N)=O)N)=O)=O)=O)N[C@H](C(O)=O)CCCNC(N)=N
Properties
Chemical formula
 C29H48N12O8
Molar mass 692.779 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

Opiorphin is an endogenous chemical compound first isolated from human saliva. Initial research with mice shows the compound has a painkilling effect greater than that of morphine.[2] It works by stopping the normal breakup of enkephalins, natural pain-killing opioids in the spinal cord. It is a relatively simple molecule consisting of a five-amino acid polypeptide, Gln-Arg-Phe-Ser-Arg (QRFSR).[3][4][5][6][7][8][9][10]

Opiorphin pentapeptide originates from the N-terminal region of the protein PROL1 (proline-rich, lacrimal 1).[3] Opiorphin inhibits three proteases: neutral ecto-endopeptidase (MME), ecto-aminopeptidase N (ANPEP)[3] and perhaps also a dipeptidyl peptidase DPP3.[8] Such action extends the duration of enkephalin effect where the natural pain killers are released physiologically in response to specific potentially painful stimuli, in contrast with administration of narcotics, which floods the entire body and causes many undesirable adverse reactions, including addiction liability and constipation.[11][12] In addition, opiorphin may exert anti-depressive[13][14] and antipanic action.[15]

Therapeutic application of opiorphin in humans would require modifying the molecule to avoid its rapid degradation in the intestine and its poor penetration of the blood–brain barrier.[11][12] This modification is done in the body by transformation of N-terminal glutamine into pyroglutamate. This form preserves the analgesic properties of opiorphin but with increased pharmaceutical stability.[16]

See also

References

  1. ↑ Opiorphin at Sigma-Aldrich
  2. ↑ Rougeot C, Robert F, Menz L, Bisson JF, Messaoudi M (August 2010). "Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects". J. Physiol. Pharmacol. 61 (4): 483–90. PMID 20814077.
  3. 1 2 3 Dickinson DP, Thiesse M (April 1996). "cDNA cloning of an abundant human lacrimal gland mRNA encoding a novel tear protein". Curr. Eye Res. 15 (4): 377–86. doi:10.3109/02713689608995828. PMID 8670737.
  4. ↑ Andy Coghlan (November 13, 2006). "Natural-born painkiller found in human saliva". New Scientist. Archived from the original on 2007-01-27.
  5. ↑ "Natural chemical 'beats morphine'". BBC News. November 14, 2006.
  6. ↑ Mary Beckman (November 13, 2006). "Prolonging Painkillers". ScienceNOW.
  7. ↑ Stanović S, Boranić M, Petrovecki M, et al. (2000). "Thiorphan, an inhibitor of neutral endopeptidase/enkephalinase (CD10/CALLA) enhances cell proliferation in bone marrow cultures of patients with acute leukemia in remission". Haematologia (Budap). 30 (1): 1–10. doi:10.1163/15685590051129814. PMID 10841318.
  8. 1 2 Thanawala V, Kadam VJ, Ghosh R (October 2008). "Enkephalinase inhibitors: potential agents for the management of pain". Curr Drug Targets. 9 (10): 887–94. doi:10.2174/138945008785909356. PMID 18855623.
  9. ↑ Davies KP (March 2009). "The role of opiorphins (endogenous neutral endopeptidase inhibitors) in urogenital smooth muscle biology". J Sex Med. 6 Suppl 3: 286–91. doi:10.1111/j.1743-6109.2008.01186.x. PMC 2864530. PMID 19267851.
  10. ↑ Tian XZ, Chen J, Xiong W, He T, Chen Q (July 2009). "Effects and underlying mechanisms of human opiorphin on colonic motility and nociception in mice". Peptides. 30 (7): 1348–54. doi:10.1016/j.peptides.2009.04.002. PMID 19442408. S2CID 32291165.
  11. 1 2 Rougeot C, Robert F, Menz L, Bisson JF, Messaoudi M (August 2010). "Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects" (PDF). J. Physiol. Pharmacol. 61 (4): 483–90. PMID 20814077.
  12. 1 2 Popik P, Kamysz E, Kreczko J, Wróbel M (November 2010). "Human opiorphin: the lack of physiological dependence, tolerance to antinociceptive effects and abuse liability in laboratory mice". Behav. Brain Res. 213 (1): 88–93. doi:10.1016/j.bbr.2010.04.045. PMID 20438769. S2CID 32205999.
  13. ↑ Javelot H, Messaoudi M, Garnier S, Rougeot C (June 2010). "Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways" (PDF). J. Physiol. Pharmacol. 61 (3): 355–62. PMID 20610867.
  14. ↑ Yang QZ, Lu SS, Tian XZ, Yang AM, Ge WW, Chen Q (February 2011). "The antidepressant-like effect of human opiorphin via opioid-dependent pathways in mice". Neurosci. Lett. 489 (2): 131–5. doi:10.1016/j.neulet.2010.12.002. PMID 21145938. S2CID 22544303.
  15. ↑ Maraschin, Jhonatan Christian; Rangel, Marcel Pereira; Bonfim, Antonio Joaquim; Kitayama, Mariana; Graeff, Frederico Guilherme; Zangrossi Jr., Hélio; Audi, Elisabeth Aparecida (2016-02-01). "Opiorphin causes a panicolytic-like effect in rat panic models mediated by μ-opioid receptors in the dorsal periaqueductal gray". Neuropharmacology. 101: 264–270. doi:10.1016/j.neuropharm.2015.09.008. PMID 26363194. S2CID 34867419.
  16. ↑ Sitbon, Philippe; Van Elstraete, Alain; Hamdi, Leila; Juarez-Perez, Victor; Mazoit, Jean-Xavier; Benhamou, Dan; Rougeot, Catherine (2016-11-01). "STR-324, a Stable Analog of Opiorphin, Causes Analgesia in Postoperative Pain by Activating Endogenous Opioid Receptor-dependent Pathways". Anesthesiology. 125 (5): 1017–1029. doi:10.1097/ALN.0000000000001320. ISSN 1528-1175. PMID 27571257. S2CID 36827893.
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