| Revision as of 19:51, 27 October 2010 editEmissrto (talk | contribs)423 editsm removed ==See Also== *Endothelin receptor antagonist← Previous edit |
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{{chembox |
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|Reference=<ref name=Sigma> at ]</ref> |
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|ImageFile=BQ-123.png |
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| verifiedrevid = 393276085 |
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|ImageSize=200px |
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| Reference = <ref name=Sigma> at ]</ref> |
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|IUPACName=2-octadecan-3-yl]acetic acid |
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| ImageFile = BQ-123 structure.svg |
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|OtherNames=Cyclo(<small>D</small>-trp-<small>D</small>-asp-<small>L</small>-pro-<small>D</small>-val-<small>L</small>-leu) |
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| IUPACName = 2-octadecan-3-yl]acetic acid |
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| OtherNames = Cyclo(<small>D</small>-trp-<small>D</small>-asp-<small>L</small>-pro-<small>D</small>-val-<small>L</small>-leu) |
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|Section1={{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| CASNo_Ref = {{cascite|correct|??}} |
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| CASNo=136553-81-6 |
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| CASNo = 136553-81-6 |
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| PubChem=443289 |
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| IUPHAR_ligand = 1003 |
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| PubChem = 443289 |
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| UNII_Ref = {{fdacite|changed|FDA}} |
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| UNII = S2A8YZM151 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 1269102 |
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| IUPHAR_ligand2 = 1003<!-- 2nd ligand not in Chembox yet --> |
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| IUPHAR_ligand = 997 |
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| IUPHAR_ligand = 997 |
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| SMILES=CC(C)C1C(=O)N(C(=O)N(C(=O)N2CCC2C(=O)N(C(=O)N1)C(C)C)CC(=O)O)CC3=CNC4=CC=CC=C43 |
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| SMILES = CC(C)C1C(=O)N(C(=O)N(C(=O)N2CCC2C(=O)N(C(=O)N1)C(C)C)CC(=O)O)CC3=CNC4=CC=CC=C43 |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| ChemSpiderID = 25069753 |
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| InChI = 1/C31H42N6O7/c1-16(2)12-21-27(40)33-22(13-18-15-32-20-9-6-5-8-19(18)20)28(41)35-23(14-25(38)39)31(44)37-11-7-10-24(37)29(42)36-26(17(3)4)30(43)34-21/h5-6,8-9,15-17,21-24,26,32H,7,10-14H2,1-4H3,(H,33,40)(H,34,43)(H,35,41)(H,36,42)(H,38,39)/t21-,22+,23-,24-,26+/m0/s1 |
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| InChIKey = VYCMAAOURFJIHD-AOYLRGCGBG |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChI = 1S/C31H42N6O7/c1-16(2)12-21-27(40)33-22(13-18-15-32-20-9-6-5-8-19(18)20)28(41)35-23(14-25(38)39)31(44)37-11-7-10-24(37)29(42)36-26(17(3)4)30(43)34-21/h5-6,8-9,15-17,21-24,26,32H,7,10-14H2,1-4H3,(H,33,40)(H,34,43)(H,35,41)(H,36,42)(H,38,39)/t21-,22+,23-,24-,26+/m0/s1 |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey = VYCMAAOURFJIHD-AOYLRGCGSA-N |
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|Section2={{Chembox Properties |
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|Section2={{Chembox Properties |
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| C=31|H=42|N=6|O=7 |
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| C=31|H=42|N=6|O=7 |
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|Section3={{Chembox Hazards |
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| SPhrases={{S22}} {{S24/25}} |
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| HPhrases = {{HPhrases|}} |
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| PPhrases = {{PPhrases|}} |
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| GHS_ref = <!-- PubChem: no GHS label found --> |
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'''BQ-123''', also known as cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-), is a cyclic pentapeptide that was first isolated from a fermentation broth of '']'' in 1991.<ref>{{cite journal | vauthors = Ihara M, Fukuroda T, Saeki T, Nishikibe M, Kojiri K, Suda H, Yano M | title = An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis | journal = Biochemical and Biophysical Research Communications | volume = 178 | issue = 1 | pages = 132–7 | date = July 1991 | pmid = 1648907 | doi = 10.1016/0006-291X(91)91789-F }}</ref> NMR studies indicate that the polypeptide backbone consists of a type II beta turn and an inverse gamma turn.<ref>{{cite journal | vauthors = Atkinson RA, Pelton JT | title = Conformational study of cyclo, an endothelin-A receptor-selective antagonist | journal = FEBS Letters | volume = 296 | issue = 1 | pages = 1–6 | date = January 1992 | pmid = 1309703 | doi = 10.1016/0014-5793(92)80390-3 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Krystek SR, Bassolino DA, Bruccoleri RE, Hunt JT, Porubcan MA, Wandler CF, Andersen NH | title = Solution conformation of a cyclic pentapeptide endothelin antagonist. Comparison of structures obtained from constrained dynamics and conformational search | journal = FEBS Letters | volume = 299 | issue = 3 | pages = 255–61 | date = March 1992 | pmid = 1544503 | doi = 10.1016/0014-5793(92)80127-3 | doi-access = free }}</ref> The side-chains adopt different orientations depending on the solvent used.<ref>{{cite journal | vauthors = Gonnella NC, Zhang X, Jin Y, Prakash O, Paris CG, Kolossváry I, Guida WC, Bohacek RS, Vlattas I, Sytwu T | display-authors = 6 | title = Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-). An NMR spectroscopy and molecular modeling study | journal = International Journal of Peptide and Protein Research | volume = 43 | issue = 5 | pages = 454–62 | date = May 1994 | pmid = 8070969 | doi = 10.1111/j.1399-3011.1994.tb00544.x }}</ref><ref>{{cite journal | vauthors = Bean JW, Peishoff CE, Kopple KD | title = Conformations of cyclic pentapeptide endothelin receptor antagonists | journal = International Journal of Peptide and Protein Research | volume = 44 | issue = 3 | pages = 223–32 | date = September 1994 | pmid = 7822098 | doi = 10.1111/j.1399-3011.1994.tb00164.x }}</ref> The proline carbonyl oxygen atom located at the onset of a beta turn is a sodium ion binding site.<ref>{{cite journal | vauthors = Ngoka LC, Gross ML | title = Location of alkali metal binding sites in endothelin A selective receptor antagonists, cyclo(D-Trp-D-Asp-Pro-D-Val-Leu) and cyclo(D-Trp-D-Asp-Pro-D-Ile-Leu), from multistep collisionally activated decompositions | journal = Journal of Mass Spectrometry | volume = 35 | issue = 2 | pages = 265–76 | date = February 2000 | pmid = 10679990 | doi = 10.1002/(SICI)1096-9888(200002)35:2<265::AID-JMS946>3.0.CO;2-# | bibcode = 2000JMSp...35..265N }}</ref> It has a high affinity for sodium ions and can coordinate up to three of them.<ref>{{cite journal | vauthors = Ngoka LC, Gross ML | title = Novel sodium binding properties of some cyclopentapeptide endothelin A selective receptor antagonists: electrospray and fast-atom-bombardment mass spectrometric studies | journal = Biochemical and Biophysical Research Communications | volume = 254 | issue = 3 | pages = 713–9 | date = January 1999 | pmid = 9920807 | doi = 10.1006/bbrc.1998.9772 }}</ref> Studies have shown that BQ123 is effective in reversing Ischemia-induced acute renal failure, and it has been suggested that this might be because BQ123 increases reabsorption of sodium ions in the proximal tubule cells.<ref>{{cite journal | vauthors = Büyükgebiz O, Aktan AO, Haklar G, Yalçin AS, Yeğen C, Yalin R, Ercan ZS | title = BQ-123, a specific endothelin (ETA) receptor antagonist, prevents ischemia-reperfusion injury in kidney transplantation | journal = Transplant International | volume = 9 | issue = 3 | pages = 201–7 | date = 1996 | pmid = 8723187 | doi = 10.1007/BF00335386 | s2cid = 39612393 }}</ref><ref>{{cite journal | vauthors = Clozel M, Watanabe H | title = BQ-123, a peptidic endothelin ETA receptor antagonist, prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not intravenous injection | journal = Life Sciences | volume = 52 | issue = 9 | pages = 825–34 | date = 1993 | pmid = 8437512 | doi = 10.1016/0024-3205(93)90081-d }}</ref><ref>{{cite journal | vauthors = Clavell AL, Stingo AJ, Margulies KB, Brandt RR, Burnett JC | title = Role of endothelin receptor subtypes in the in vivo regulation of renal function | journal = The American Journal of Physiology | volume = 268 | issue = 3 Pt 2 | pages = F455-60 | date = March 1995 | pmid = 7900845 | doi = 10.1152/ajprenal.1995.268.3.F455 }}</ref><ref>{{cite journal | vauthors = Gellai M, Jugus M, Fletcher T, DeWolf R, Nambi P | title = Reversal of postischemic acute renal failure with a selective endothelinA receptor antagonist in the rat | journal = The Journal of Clinical Investigation | volume = 93 | issue = 2 | pages = 900–6 | date = February 1994 | pmid = 8113422 | pmc = 293964 | doi = 10.1172/JCI117046 }}</ref><ref>{{cite journal | vauthors = Mino N, Kobayashi M, Nakajima A, Amano H, Shimamoto K, Ishikawa K, Watanabe K, Nishikibe M, Yano M, Ikemoto F | display-authors = 6 | title = Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats | journal = European Journal of Pharmacology | volume = 221 | issue = 1 | pages = 77–83 | date = October 1992 | pmid = 1459192 | doi = 10.1016/0014-2999(92)90774-x }}</ref> |
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'''BQ-123''' is a ] consisting of five ]s. The amino acid sequence is <small>D</small>-]-<small>D</small>-]-<small>L</small>-]-<small>D</small>-]-<small>L</small>-]. |
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BQ-123 is a selective ET<sub>A</sub> ].<ref name="Sigma"/><ref name="JAntibiot1987-Kino">{{cite journal | vauthors = Ishikawa K, Fukami T, Nagase T, Fujita K, Hayama T, Niiyama K, Mase T, Ihara M, Yano M | display-authors = 6 | title = Cyclic pentapeptide endothelin antagonists with high ETA selectivity. Potency- and solubility-enhancing modifications | journal = Journal of Medicinal Chemistry | volume = 35 | issue = 11 | pages = 2139–42 | date = May 1992 | pmid = 1317926 | doi = 10.1021/jm00089a028 }}</ref> As such, it is used as a biochemical tool in the study of ] function. BQ-123 works as an ET-1 antagonist by reversing already established contractions to ET-1. This indicates that BQ-123 can work as an antagonist to remove ET-1 from its receptor (ET<sub>A</sub>).<ref>{{cite journal | vauthors = Berrazueta JR, Bhagat K, Vallance P, MacAllister RJ | title = Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm | journal = British Journal of Clinical Pharmacology | volume = 44 | issue = 6 | pages = 569–71 | date = December 1997 | pmid = 9431833 | pmc = 2042881 | doi = 10.1046/j.1365-2125.1997.t01-1-00631.x }}</ref> |
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BQ-123 is a selective ET<sub>A</sub> ].<ref name="Sigma"/> As such, it is used as a biochemical tool in the study of endothelin receptor function. |
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==References== |
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== References == |
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