KGOP01

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KGOP01
Clinical data
Other names2,6-Dimethyl-L-tyrosyl-N-[(4S)-2-(3-amino-3-oxopropyl)-3-oxo-2,3,4,5-tetrahydro-1H-2-benzazepin-4-yl]-D-argininamide
Identifiers
  • (2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-N-[(4S)-2-(3-amino-3-oxopropyl)-3-oxo-4,5-dihydro-1H-2-benzazepin-4-yl]-5-(diaminomethylideneamino)pentanamide
PubChem CID
ChemSpider
ChEMBL
Chemical and physical data
FormulaC30H42N8O5
Molar mass594.717 g·mol−1
3D model (JSmol)
  • CC1=CC(=CC(=C1C[C@@H](C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H]2CC3=CC=CC=C3CN(C2=O)CCC(=O)N)N)C)O
  • InChI=1S/C30H42N8O5/c1-17-12-21(39)13-18(2)22(17)15-23(31)27(41)36-24(8-5-10-35-30(33)34)28(42)37-25-14-19-6-3-4-7-20(19)16-38(29(25)43)11-9-26(32)40/h3-4,6-7,12-13,23-25,39H,5,8-11,14-16,31H2,1-2H3,(H2,32,40)(H,36,41)(H,37,42)(H4,33,34,35)/t23-,24+,25-/m0/s1
  • Key:VBTIGXSUDIFYPI-GVAUOCQISA-N

KGOP01 (H-Dmt-d-Arg-Aba-β-Ala-NH2) is a synthetic peptide derivative which acts as a potent agonist of opioid receptors and has analgesic effects.[1] It was originally derived from modification of dermorphin, a naturally occurring opioid peptide secreted by some species of South American frogs.[1]

While numerous opioid peptides are known and widely used in scientific research, such as DAMGO and DADLE, these are rapidly metabolised in the body and fail to cross the blood-brain barrier, and so do not produce centrally mediated analgesic effects.[1] KGOP01 on the other hand contains several unnatural amino acids and is both metabolically stable and able to enter the brain, resulting in potent analgesic effects in animal studies.[1]

Because it is a peptide, it can be readily hybridised with other peptide ligands and so has been widely used to produce hybrid compounds combining opioid activity with activity at receptors for neuropeptides such as nociceptin, neurokinin, neurotensin and neuropeptide FF, which may lead to the development of improved opioid analgesics with reduced side effects.[2][3][4][5][6]

See also

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References

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  1. ^ a b c d Dumitrascuta M, Bermudez M, Ballet S, Wolber G, Spetea M (April 2020). "Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt1]DALDA, and KGOP01, Binding to the mu Opioid Receptor". Molecules. 25 (9): 2087. doi:10.3390/molecules25092087. PMC 7248707. PMID 32365707.
  2. ^ Guillemyn K, Kleczkowska P, Lesniak A, Dyniewicz J, Van der Poorten O, Van den Eynde I, et al. (March 2015). "Synthesis and biological evaluation of compact, conformationally constrained bifunctional opioid agonist - neurokinin-1 antagonist peptidomimetics". European Journal of Medicinal Chemistry. 92: 64–77. doi:10.1016/j.ejmech.2014.12.033. PMC 4336569. PMID 25544687.
  3. ^ Guillemyn K, Starnowska J, Lagard C, Dyniewicz J, Rojewska E, Mika J, et al. (April 2016). "Bifunctional Peptide-Based Opioid Agonist-Nociceptin Antagonist Ligands for Dual Treatment of Acute and Neuropathic Pain". Journal of Medicinal Chemistry. 59 (8): 3777–3792. doi:10.1021/acs.jmedchem.5b01976. PMC 4850106. PMID 27035422.
  4. ^ Drieu la Rochelle A, Guillemyn K, Dumitrascuta M, Martin C, Utard V, Quillet R, et al. (September 2018). "A bifunctional-biased mu-opioid agonist-neuropeptide FF receptor antagonist as analgesic with improved acute and chronic side effects". Pain. 159 (9): 1705–1718. doi:10.1097/j.pain.0000000000001262. PMID 29708942.
  5. ^ Gonzalez S, Dumitrascuta M, Eiselt E, Louis S, Kunze L, Blasiol A, et al. (November 2020). "Optimized Opioid-Neurotensin Multitarget Peptides: From Design to Structure-Activity Relationship Studies". Journal of Medicinal Chemistry. 63 (21): 12929–12941. doi:10.1021/acs.jmedchem.0c01376. PMC 7667639. PMID 32902268.
  6. ^ Gadais C, Piekielna-Ciesielska J, De Neve J, Martin C, Janecka A, Ballet S (September 2021). "Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics". Molecules. 26 (17): 5406. doi:10.3390/molecules26175406. PMC 8434392. PMID 34500841.