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DALDA

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For the vegetable oil, see Dalda.
DALDA
Clinical data
Other namesDermorphin [D-Arg2, Lys4] (1-4) Amide
Identifiers
  • (2S)-6-amino-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-phenylpropanoyl]amino]hexanamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC30H45N9O5
Molar mass611.748 g·mol−1
3D model (JSmol)
  • C1=CC=C(C=C1)C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N)NC(=O)[C@@H](CCCN=C(N)N)NC(=O)[C@H](CC2=CC=C(C=C2)O)N
  • InChI=1S/C30H45N9O5/c31-15-5-4-9-23(26(33)41)37-29(44)25(18-19-7-2-1-3-8-19)39-28(43)24(10-6-16-36-30(34)35)38-27(42)22(32)17-20-11-13-21(40)14-12-20/h1-3,7-8,11-14,22-25,40H,4-6,9-10,15-18,31-32H2,(H2,33,41)(H,37,44)(H,38,42)(H,39,43)(H4,34,35,36)/t22-,23-,24+,25-/m0/s1
  • Key:UEVAHGMTRWGMTB-JBXUNAHCSA-N

DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) is a synthetic peptide derivative which acts as a potent and highly selective agonist of the mu opioid receptor. It was originally derived as a more metabolically stable analogue of dermorphin, a naturally occurring opioid peptide secreted by some species of South American frogs.[1][2][3] DALDA is unable to cross the blood-brain barrier, making it highly peripherally selective, but it has been researched for the treatment of colitis and neuropathic pain, where peripheral opioid agonism is able to produce analgesic effects in the absence of central opioid receptor activation.[4][5][6][7][8][9][10][11][12] Some derivatives of DALDA such as [Dmt1]DALDA (where the tyrosine residue has been substituted with 2,6-dimethyl groups) or more complexly modified derivatives such as KGOP01, do however cross the blood-brain barrier and produce typical opioid effects.[13][14][15][16][17][18][19][20]

[Dmt1]DALDA, CAS# 255861-98-4 PMID 9809562

References

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  1. ^ Schiller PW, Nguyen TM, Chung NN, Lemieux C (March 1989). "Dermorphin analogues carrying an increased positive net charge in their "message" domain display extremely high mu opioid receptor selectivity". Journal of Medicinal Chemistry. 32 (3): 698–703. doi:10.1021/jm00123a035. PMID 2537427.
  2. ^ Szeto HH, Lovelace JL, Fridland G, Soong Y, Fasolo J, Wu D, et al. (July 2001). "In vivo pharmacokinetics of selective mu-opioid peptide agonists". The Journal of Pharmacology and Experimental Therapeutics. 298 (1): 57–61. doi:10.1016/S0022-3565(24)29351-4. PMID 11408525.
  3. ^ Rodziewicz-Motowidło S, Czaplewski C, Luczak S, Ciarkowski J (August 2008). "Conformation-activity relationships of cyclo-constrained micro/delta opioid agonists derived from the N-terminal tetrapeptide segment of dermorphin/deltorphin". Journal of Peptide Science. 14 (8): 898–902. doi:10.1002/psc.1022. PMID 18338322.
  4. ^ Philippe D, Dubuquoy L, Groux H, Brun V, Chuoï-Mariot MT, Gaveriaux-Ruff C, et al. (May 2003). "Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation". The Journal of Clinical Investigation. 111 (9): 1329–1338. doi:10.1172/JCI16750. PMC 154442. PMID 12727924.
  5. ^ Tiwari V, Yang F, He SQ, Shechter R, Zhang C, Shu B, et al. (March 2016). "Activation of Peripheral μ-opioid Receptors by Dermorphin [D-Arg2, Lys4] (1-4) Amide Leads to Modality-preferred Inhibition of Neuropathic Pain". Anesthesiology. 124 (3): 706–720. doi:10.1097/ALN.0000000000000993. PMC 4755859. PMID 26756519.
  6. ^ Barpujari A, Ford N, He SQ, Huang Q, Gaveriaux-Ruff C, Dong X, et al. (November 2020). "Role of peripheral sensory neuron mu-opioid receptors in nociceptive, inflammatory, and neuropathic pain". Regional Anesthesia and Pain Medicine. 45 (11): 907–916. doi:10.1136/rapm-2020-101779. PMC 8692009. PMID 32928995.
  7. ^ Xu B, Zhang Q, Chen D, Zhang M, Zhang R, Zhao W, et al. (February 2023). "OCP002, a Mixed Agonist of Opioid and Cannabinoid Receptors, Produces Potent Antinociception With Minimized Side Effects". Anesthesia and Analgesia. 136 (2): 373–386. doi:10.1213/ANE.0000000000006266. PMID 36638515.
  8. ^ Gadepalli A, Ummadisetty O, Chouhan D, Yadav KE, Tiwari V (January 2024). "Peripheral mu-opioid receptor activation by dermorphin [D-Arg2, Lys4] (1-4) amide alleviates behavioral and neurobiological aberrations in rat model of chemotherapy-induced neuropathic pain". Neurotherapeutics. 21 (1) e00302. doi:10.1016/j.neurot.2023.10.012. PMC 10903092. PMID 38241153.
  9. ^ Ummadisetty O, Gadepalli A, Chouhan D, Patil U, Singh SP, Singh S, et al. (August 2024). "Dermorphin [D-Arg2, Lys4] (1-4) Amide Alleviates Frostbite-Induced Pain by Regulating TRP Channel-Mediated Microglial Activation and Neuroinflammation". Molecular Neurobiology. 61 (8): 6089–6100. doi:10.1007/s12035-024-03949-4. PMID 38277118.
  10. ^ Limerick G, Uniyal A, Ford N, He S, Grenald SA, Zhang C, et al. (November 2024). "Peripherally restricted cannabinoid and mu-opioid receptor agonists synergistically attenuate neuropathic mechanical hypersensitivity in mice". Pain. 165 (11): 2563–2577. doi:10.1097/j.pain.0000000000003278. PMC 11511654. PMID 38815196.
  11. ^ Wu Q, Ford NC, He S, Zhang C, Cui X, Liu J, et al. (March 2025). "Characterizing a new rat model of chronic pain after spine surgery". Bone Research. 13 (1) 34. doi:10.1038/s41413-025-00408-1. PMC 11904174. PMID 40074742.
  12. ^ Modi A, Uniyal A, Tiwari V, Chouhan D, Agrawal S, Ummadisetty O, et al. (October 2025). "Dermorphin [D-Arg2, Lys4] (1-4) Amide Attenuates Burn Pain by Inhibiting TRPV1/NR2B Mediated Neuroinflammatory Signalling". Molecular Neurobiology. 62 (10): 12668–12687. doi:10.1007/s12035-025-05068-0. PMID 40442534.
  13. ^ Schiller PW, Nguyen TM, Berezowska I, Dupuis S, Weltrowska G, Chung NN, et al. (October 2000). "Synthesis and in vitro opioid activity profiles of DALDA analogues". European Journal of Medicinal Chemistry. 35 (10): 895–901. doi:10.1016/s0223-5234(00)01171-5. PMID 11121615.
  14. ^ Shimoyama M, Shimoyama N, Zhao GM, Schiller PW, Szeto HH (April 2001). "Antinociceptive and respiratory effects of intrathecal H-Tyr-D-Arg-Phe-Lys-NH2 (DALDA) and [Dmt1] DALDA". The Journal of Pharmacology and Experimental Therapeutics. 297 (1): 364–371. doi:10.1016/S0022-3565(24)29547-1. PMID 11259564.
  15. ^ Neilan CL, Nguyen TM, Schiller PW, Pasternak GW (May 2001). "Pharmacological characterization of the dermorphin analog [Dmt(1)]DALDA, a highly potent and selective mu-opioid peptide". European Journal of Pharmacology. 419 (1): 15–23. doi:10.1016/s0014-2999(01)00946-3. PMID 11348625.
  16. ^ Schiller PW (October 2005). "Opioid peptide-derived analgesics". The AAPS Journal. 7 (3): E560 – E565. doi:10.1208/aapsj070356. PMC 2751258. PMID 16353933.
  17. ^ Schiller PW (April 2010). "Bi- or multifunctional opioid peptide drugs". Life Sciences. 86 (15–16): 598–603. doi:10.1016/j.lfs.2009.02.025. PMC 2848892. PMID 19285088.
  18. ^ Shimoyama M, Schiller PW, Shimoyama N, Toyama S, Szeto HH (November 2012). "Superior analgesic effect of H-Dmt-D-Arg-Phe-Lys-NH2 ([Dmt1]DALDA), a multifunctional opioid peptide, compared to morphine in a rat model of neuropathic pain". Chemical Biology & Drug Design. 80 (5): 771–774. doi:10.1111/cbdd.12003. PMC 3465489. PMID 22834682.
  19. ^ 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.
  20. ^ Choi TL, Lau MY, Wong JK, Wan TS, Ho EN (March 2024). "Identification of the dermorphin tetrapeptide [Dmt1 ]-DALDA in a seized unlabelled vial and its first detection in horse urine: A case report". Drug Testing and Analysis. 16 (3): 268–276. doi:10.1002/dta.3536. PMID 37408356.
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