DBI33-50

DBI33-50
Identifiers
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
FormulaC80H126N20O30S
Molar mass1880.06 g·mol−1
3D model (JSmol)
  • C[C@H]([C@@H](C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)N)N)O
  • InChI=1S/C81H138N24O29/c1-35(2)26-46(67(120)96-48(28-37(5)6)69(122)98-51(31-59(114)115)71(124)97-47(27-36(3)4)68(121)95-45(80(133)134)18-14-15-23-82)92-56(110)33-89-74(127)53-20-17-25-105(53)79(132)44(19-16-24-88-81(86)87)94-70(123)52(32-60(116)117)100-77(130)63(41(12)106)104-72(125)49(29-55(85)109)99-76(129)62(39(9)10)101-73(126)50(30-58(112)113)93-57(111)34-90-75(128)61(38(7)8)102-78(131)64(42(13)107)103-65(118)40(11)91-66(119)43(83)21-22-54(84)108/h35-53,61-64,106-107H,14-34,82-83H2,1-13H3,(H2,84,108)(H2,85,109)(H,89,127)(H,90,128)(H,91,119)(H,92,110)(H,93,111)(H,94,123)(H,95,121)(H,96,120)(H,97,124)(H,98,122)(H,99,129)(H,100,130)(H,101,126)(H,102,131)(H,103,118)(H,104,125)(H,112,113)(H,114,115)(H,116,117)(H,133,134)(H4,86,87,88)/t40-,41+,42+,43-,44-,45-,46-,47-,48-,49-,50-,51-,52-,53-,61-,62-,63-,64-/m0/s1
  • Key:PTVIBIVJSXWMPT-FGSANIJTSA-N

DBI33-50 (Octadecaneuropeptide, ODN) is an endogenous polypeptide with the amino acid sequence QATVGDINTERPGMLDFT. It consists of residues 33–50 of the diazepam binding inhibitor (DBI), generated by proteolytic cleavage of the parent protein. A related fragment, DBI17-50 (triakontatetraneuropeptide, TTN), shares similar biological effects but is expressed in different tissues.[1]

DBI itself is highly expressed in the gastrointestinal tract, where it inhibits the secretion of hormones such as insulin and cholecystokinin. ODN (but not TTN) also suppresses insulin release. However, both peptides are more widely studied as neuropeptides in the brain, where they are secreted by astrocytes and act as endogenous allosteric modulators of benzodiazepine receptors (endozepines). ODN primarily acts at the central benzodiazepine receptor, while TTN preferentially targets the so-called peripheral benzodiazepine receptor (TSPO), which is also present in the brain.[2][3][4][5][6]

In addition to its benzodiazepine site activity, ODN binds to a distinct metabotropic receptor. At benzodiazepine receptors it displays a biphasic action: at low concentrations it acts as a positive allosteric modulator, mainly at α5-containing GABAA receptor subtypes, whereas at higher concentrations it acts as a negative allosteric modulator, particularly at α3-containing GABAA receptors.[7][8]

Pathologically elevated ODN levels can therefore produce effects opposite to those of benzodiazepines, and have been linked to anxiety and epilepsy. At normal physiological concentrations, by contrast, ODN is neuroprotective, promotes neurogenesis, and regulates immune responses by modulating interleukin production. Disruption of ODN signaling is thought to contribute to adverse effects associated with long-term benzodiazepine use, including cognitive impairment and delayed wound healing.[9][10][6][11][12][13][14][15][16]

References

  1. ^ Borboni P, Condorelli L, De Stefanis P, Sesti G, Lauro R (December 1991). "Modulation of insulin secretion by diazepam binding inhibitor and its processing products". Neuropharmacology. 30 (12B): 1399–1403. doi:10.1016/s0028-3908(11)80008-0. PMID 1664067.
  2. ^ De Stefanis P, Impagnatiello F, Berkovich A, Guidotti A (April 1995). "Inhibitory effect of ODN, a naturally occurring processing product of diazepam binding inhibitor, on secretagogues-induced insulin secretion". Regulatory Peptides. 56 (2–3): 153–165. doi:10.1016/0167-0115(95)00002-s. PMID 7544471.
  3. ^ do Rego JC, Orta MH, Leprince J, Tonon MC, Vaudry H, Costentin J (July 2007). "Pharmacological characterization of the receptor mediating the anorexigenic action of the octadecaneuropeptide: evidence for an endozepinergic tone regulating food intake". Neuropsychopharmacology. 32 (7): 1641–1648. doi:10.1038/sj.npp.1301280. PMID 17151595.
  4. ^ Do Rego JL, Seong JY, Burel D, Luu-The V, Larhammar D, Tsutsui K, et al. (April 2009). "Steroid biosynthesis within the frog brain: a model of neuroendocrine regulation". Annals of the New York Academy of Sciences. 1163: 83–92. doi:10.1111/j.1749-6632.2008.03664.x. PMID 19456330.
  5. ^ Clavier T, Tonon MC, Foutel A, Besnier E, Lefevre-Scelles A, Morin F, et al. (November 2014). "Increased plasma levels of endozepines, endogenous ligands of benzodiazepine receptors, during systemic inflammation: a prospective observational study". Critical Care. 18 (6) 633. doi:10.1186/s13054-014-0633-7. PMC 4326502. PMID 25407756.
  6. ^ a b Tonon MC, Vaudry H, Chuquet J, Guillebaud F, Fan J, Masmoudi-Kouki O, et al. (April 2020). "Endozepines and their receptors: Structure, functions and pathophysiological significance". Pharmacology & Therapeutics. 208 107386. doi:10.1016/j.pharmthera.2019.06.008. PMID 31283949.
  7. ^ Möhler H (June 2014). "Endogenous benzodiazepine site peptide ligands operating bidirectionally in vivo in neurogenesis and thalamic oscillations". Neurochemical Research. 39 (6): 1032–1036. doi:10.1007/s11064-014-1303-5. PMID 24715673.
  8. ^ Hazime M, Gasselin M, Alasoadura M, Leclerc J, Lefranc B, Basille-Dugay M, et al. (August 2025). "Dose-Dependent Dual Effect of the Endozepine ODN on Neuronal Spiking Activity". Brain Sciences. 15 (8): 885. doi:10.3390/brainsci15080885. PMC 12384177. PMID 40867217.
  9. ^ Stepień H, Agro A, Crossley J, Padol I, Richards C, Stanisz A (September 1993). "Immunomodulatory properties of diazepam-binding inhibitor: effect on human interleukin-6 secretion, lymphocyte proliferation and natural killer cell activity in vitro". Neuropeptides. 25 (3): 207–211. doi:10.1016/0143-4179(93)90104-i. PMID 8247258.
  10. ^ Masmoudi-Kouki O, Hamdi Y, Ghouili I, Bahdoudi S, Kaddour H, Leprince J, et al. (2019). "Neuroprotection with the Endozepine Octadecaneuropeptide, ODN". review. Current Pharmaceutical Design. 24 (33): 3918–3925. doi:10.2174/1381612824666181112111746. PMID 30417780.
  11. ^ Masmoudi-Kouki O, Namsi A, Hamdi Y, Bahdoudi S, Ghouili I, Chuquet J, et al. (2020). "Cytoprotective and Neurotrophic Effects of Octadecaneuropeptide (ODN) in in vitro and in vivo Models of Neurodegenerative Diseases". review. Frontiers in Endocrinology. 11 566026. doi:10.3389/fendo.2020.566026. PMC 7672186. PMID 33250858.
  12. ^ Lamtahri R, Hazime M, Gowing EK, Nagaraja RY, Maucotel J, Alasoadura M, et al. (August 2021). "The Gliopeptide ODN, a Ligand for the Benzodiazepine Site of GABAA Receptors, Boosts Functional Recovery after Stroke". The Journal of Neuroscience. 41 (33): 7148–7159. doi:10.1523/JNEUROSCI.2255-20.2021. PMC 8372017. PMID 34210784.
  13. ^ He Y, Li J, Yi L, Li X, Luo M, Pang Y, et al. (2023). "Octadecaneuropeptide Ameliorates Cognitive Impairments Through Inhibiting Oxidative Stress in Alzheimer's Disease Models". Journal of Alzheimer's Disease. 92 (4): 1413–1426. doi:10.3233/JAD-221115. PMID 36911940.
  14. ^ Bourzam A, Hamdi Y, Bahdoudi S, Duraisamy K, El Mehdi M, Basille-Dugay M, et al. (July 2024). "Octadecaneuropeptide, ODN, Promotes Cell Survival against 6-OHDA-Induced Oxidative Stress and Apoptosis by Modulating the Expression of miR-34b, miR-29a, and miR-21in Cultured Astrocytes". Cells. 13 (14): 1188. doi:10.3390/cells13141188. PMC 11487398. PMID 39056770.
  15. ^ New LE, Wang N, Khan S, Griffiths JC, Hains R, Johnston J, et al. (2024). "Insulin evokes release of endozepines from astrocytes of the NTS to modulate glucose metabolism". bioRxiv 10.1101/2024.05.03.592384.
  16. ^ Al-Mashhadani S, Sallemi M, Namsi A, Hamdi Y, Cherif A, Abidi F, et al. (January 2025). "Octadecaneuropeptide promotes the migration of astrocyte via ODN metabotropic receptor and calcium signaling pathway". Peptides. 183 171338. doi:10.1016/j.peptides.2024.171338. PMID 39755258.
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