peptide 14 [PMID: 36580549]   Click here for help

GtoPdb Ligand ID: 12333

Compound class: Peptide
Comment: This is a synthetic macrocyclic peptide that was designed to disrupt the protein-protein interaction between postsynaptic density protein-95 (PSD-95; gene symbol DLG4) and neuronal nitric oxide synthase (nNOS) [1], as a mechanism to disrupt the excitotoxic signaling and cell death that's induced (in acute ischaemia) by formation of the tri-protein complex of glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B; GluN2B or NR2B), PSD-95 and nNOS. Structurally it mimics the β-hairpin motif of nNOS that forms the interaction with the PDZ2 domain of PSD-95.
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES NCCCC[C@@H]1NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](Cc2ccccc2)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]2N(C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC1=O)[C@H](O)C)[C@H](CC)C)CCCNC(=N)N)C(C)C)[C@H](O)C)CCC(=O)N)CCC2)CCC(=O)N)[C@H](O)C)Cc1cnc[nH]1)[C@H](O)C)[C@H](O)C)[C@H](O)C)[C@H](O)C
Isomeric SMILES O=C1N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@H](CC)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)N)C(=O)N2CCC[C@@H]2C(=O)NCC(=O)N[C@H](C(=O)N[C@H]1[C@@H](C)O)CCC(=O)N)CC(=O)O)C)Cc1ccccc1)Cc1cnc[nH]1
InChI InChI=1S/C108H173N31O36/c1-15-50(6)79-99(167)123-62(27-21-37-115-108(112)113)89(157)130-78(49(4)5)98(166)136-82(54(10)142)101(169)124-65(31-34-73(111)148)106(174)138-38-22-28-70(138)96(164)117-45-74(149)120-63(30-33-72(110)147)91(159)132-81(53(9)141)102(170)128-68(42-60-44-114-47-118-60)94(162)126-66(40-48(2)3)93(161)121-64(32-35-76(151)152)92(160)134-85(57(13)145)105(173)137-83(55(11)143)103(171)127-67(41-59-24-17-16-18-25-59)95(163)135-80(52(8)140)100(168)119-51(7)87(155)125-69(43-77(153)154)88(156)116-46-75(150)129-86(58(14)146)107(175)139-39-23-29-71(139)97(165)122-61(26-19-20-36-109)90(158)133-84(56(12)144)104(172)131-79/h16-18,24-25,44,47-58,61-71,78-86,140-146H,15,19-23,26-43,45-46,109H2,1-14H3,(H2,110,147)(H2,111,148)(H,114,118)(H,116,156)(H,117,164)(H,119,168)(H,120,149)(H,121,161)(H,122,165)(H,123,167)(H,124,169)(H,125,155)(H,126,162)(H,127,171)(H,128,170)(H,129,150)(H,130,157)(H,131,172)(H,132,159)(H,133,158)(H,134,160)(H,135,163)(H,136,166)(H,137,173)(H,151,152)(H,153,154)(H4,112,113,115)/t50-,51-,52+,53+,54+,55+,56+,57+,58+,61-,62-,63-,64-,65-,66-,67-,68-,69-,70+,71-,78-,79-,80-,81-,82-,83-,84-,85-,86-/m0/s1
InChI Key XRFRKHKXUPWIIL-HAOGKZSMSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Balboa JR, Essig DJ, Ma S, Karer N, Clemmensen LS, Pedersen SW, Joerger AC, Knapp S, Østergaard S, Strømgaard K. (2023)
Development of a Potent Cyclic Peptide Inhibitor of the nNOS/PSD-95 Interaction.
J Med Chem, 66 (1): 976-990. [PMID:36580549]