Lyn peptide inhibitorInhibits Lyn activation via hematopoietin βc receptor; cell-permeable CAS# 222018-18-0 |
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Quality Control & MSDS
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| Cas No. | 222018-18-0 | SDF | Download SDF |
| PubChem ID | 102586615 | Appearance | Powder |
| Formula | C115H184N30O24 | M.Wt | 2370.91 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | Soluble to 10 mg/ml in water | ||
| Sequence | YGYRLRRKWEEKIPNP (Modifications: Tyr-1 = Octadecanoyl-Tyr, Pro-16 = C-terminal amide) | ||
| SMILES | CCCCCCCCCCCCCCCCCC(=O)NC(CC1=CC=C(C=C1)O)C(=O)NCC(=O)NC(CC2=CC=C(C=C2)O)C(=O)NC(CCCNC(=N)N)C(=O)NC(CC(C)C)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCNC(=N)N)C(=O)NC(CCCCN)C(=O)NC(CC3=CNC4=CC=CC=C43)C(=O)NC(CCC(=O)O)C(=O)NC(CCC(=O)O)C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)N5CCCC5C(=O)NC(CC(=O)N)C(=O)N6CCCC6C(=O)N | ||
| Standard InChIKey | MITSVNFZLBORMW-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C115H184N30O24/c1-6-8-9-10-11-12-13-14-15-16-17-18-19-20-21-42-93(149)131-86(63-71-43-47-74(146)48-44-71)99(156)130-68-94(150)132-87(64-72-45-49-75(147)50-46-72)108(165)137-82(39-30-59-128-115(124)125)103(160)140-85(62-69(3)4)107(164)136-81(38-29-58-127-114(122)123)101(158)135-80(37-28-57-126-113(120)121)100(157)133-78(35-24-26-55-116)102(159)141-88(65-73-67-129-77-34-23-22-33-76(73)77)109(166)139-84(52-54-96(153)154)105(162)138-83(51-53-95(151)152)104(161)134-79(36-25-27-56-117)106(163)143-97(70(5)7-2)112(169)145-61-32-41-91(145)110(167)142-89(66-92(118)148)111(168)144-60-31-40-90(144)98(119)155/h22-23,33-34,43-50,67,69-70,78-91,97,129,146-147H,6-21,24-32,35-42,51-66,68,116-117H2,1-5H3,(H2,118,148)(H2,119,155)(H,130,156)(H,131,149)(H,132,150)(H,133,157)(H,134,161)(H,135,158)(H,136,164)(H,137,165)(H,138,162)(H,139,166)(H,140,160)(H,141,159)(H,142,167)(H,143,163)(H,151,152)(H,153,154)(H4,120,121,126)(H4,122,123,127)(H4,124,125,128) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Cell-permeable inhibitor of Lyn-dependent effects of the IL-5 receptor. Blocks binding of Lyn tyrosine kinase to βc subunit of IL-3/GM-CSF/IL-5 receptors, blocking Lyn activation. Inhibits IL-5 receptor-mediated eosinophil differentiation and survival in vitro. Inhibits airway eosinophilic inflammation in mouse model of asthma. |
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A novel Lyn-binding peptide inhibitor blocks eosinophil differentiation, survival, and airway eosinophilic inflammation.[Pubmed:10395690]
J Immunol. 1999 Jul 15;163(2):939-46.
Receptor antagonists block all receptor-coupled signaling pathways indiscriminately. We introduce a novel class of peptide inhibitors that is designed to block a specific signal from a receptor while keeping other signals intact. This concept was tested in the model of IL-5 signaling via Lyn kinase. We have previously mapped the Lyn-binding site of the IL-5/GM-CSF receptor common beta (beta c) subunit. In the present study, we designed a peptide inhibitor using the Lyn-binding sequence. The peptide was N-stearated to enable cellular internalization. The stearated peptide blocked the binding of Lyn to the beta c receptor and the activation of Lyn. The lipopeptide did not affect the activation of Janus kinase 2 or its association with beta c. The inhibitor blocked the Lyn-dependent functions of IL-5 in vitro (e.g., eosinophil differentiation from stem cells and eosinophil survival). It did not affect eosinophil degranulation. When applied in vivo, the Lyn-binding peptide significantly inhibited airway eosinophil influx in a mouse model of asthma. The lipopeptide had no effect on basophil histamine release or on the proliferation of B cells and T cells. To our knowledge, this is the first report on an inhibitor of IL-5 that blocks eosinophil differentiation, survival, and airway eosinophilic inflammation. This novel strategy to develop peptide inhibitors can be applied to other receptors.
The mapping of the Lyn kinase binding site of the common beta subunit of IL-3/granulocyte-macrophage colony-stimulating factor/IL-5 receptor.[Pubmed:9973406]
J Immunol. 1999 Feb 1;162(3):1496-501.
It has been shown that a membrane-proximal region within common beta (betac) receptor of IL-3/granulocyte-macrophage CSF/IL-5 (amino acids 450-517) is important for Lyn binding. We have shown previously that Lyn kinase is physically associated with the IL-5R betac subunit in unstimulated cells. The result suggests that this association involves binding modules that are not activation or phosphorylation dependent. The objective of this study was to map the exact Lyn binding site on betac. Using overlapping and/or sequential peptides derived from betac 450-517, we narrowed down the Lyn binding site to nine amino acid residues, betac 457-465. The P-->A mutation in this region abrogated the binding to Lyn, indicating a critical role of proline residues. We created a cell-permeable Lyn-binding peptide by N-stearation. This cell-permeable peptide blocked the association of Lyn, but not Jak2 with betac in situ. We also investigated the betac binding site of Lyn kinase. Our results suggest that the N-terminal unique domain of Lyn kinase is important for binding to betac receptor. To our knowledge, this is the first molecular identification of the Lyn binding site of betac receptor. This finding may help develop specific inhibitors of Lyn-coupled signaling pathways.
