BQ-123

Last updated
BQ-123 [1]
BQ-123 structure.svg
Names
IUPAC name
2-[(3R,6R,9S,12R,15S)-6-(1H-indol-3-ylmethyl)-9-(2-methylpropyl)-2,5,8,11,14-pentaoxo-12-propan-2-yl-1,4,7,10,13-pentazabicyclo[13.3.0]octadecan-3-yl]acetic acid
Other names
Cyclo(D-trp-D-asp-L-pro-D-val-L-leu)
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
PubChem CID
UNII
  • InChI=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 X mark.svgN
    Key: VYCMAAOURFJIHD-AOYLRGCGSA-N X mark.svgN
  • 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
    Key: VYCMAAOURFJIHD-AOYLRGCGBG
  • CC(C)C[C@H]1C(=O)N[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](C(=O)N1)C(C)C)CC(=O)O)CC3=CNC4=CC=CC=C43
Properties
C31H42N6O7
Molar mass 610.712 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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 Streptomyces misakiensis in 1991. [2] NMR studies indicate that the polypeptide backbone consists of a type II beta turn and an inverse gamma turn. [3] [4] The side-chains adopt different orientations depending on the solvent used. [5] [6] The proline carbonyl oxygen atom located at the onset of a beta turn is a sodium ion binding site. [7] It has a high affinity for sodium ions and can coordinate up to three of them. [8] 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. [9] [10] [11] [12] [13]

BQ-123 is a selective ETA endothelin receptor antagonist. [1] [14] As such, it is used as a biochemical tool in the study of endothelin receptor 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 (ETA). [15]

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

<span class="mw-page-title-main">Angiotensin</span> Group of peptide hormones in mammals

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

<span class="mw-page-title-main">Agonist</span> Chemical which binds to and activates a biochemical receptor

An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agonist, while an inverse agonist causes an action opposite to that of the agonist.

<span class="mw-page-title-main">Gramicidin</span> Mix of ionophoric antibiotics

Gramicidin, also called gramicidin D, is a mix of ionophoric antibiotics, gramicidin A, B and C, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2 isoforms, so the mix has 6 different types of gramicidin molecules. They can be extracted from Brevibacillus brevis soil bacteria. Gramicidins are linear peptides with 15 amino acids. This is in contrast to unrelated gramicidin S, which is a cyclic peptide.

<span class="mw-page-title-main">Sitaxentan</span> Chemical compound

Sitaxentan sodium (TBC-11251) is a medication for the treatment of pulmonary arterial hypertension (PAH). It was marketed as Thelin by Encysive Pharmaceuticals until Pfizer purchased Encysive in February 2008. In 2010, Pfizer voluntarily removed sitaxentan from the market due to concerns about liver toxicity.

An endothelin receptor antagonist (ERA) is a drug that blocks endothelin receptors.

<span class="mw-page-title-main">Endothelin</span>

Endothelins are peptides with receptors and effects in many body organs. Endothelin constricts blood vessels and raises blood pressure. The endothelins are normally kept in balance by other mechanisms, but when overexpressed, they contribute to high blood pressure (hypertension), heart disease, and potentially other diseases.

A tetrapeptide is a peptide, classified as an oligopeptide, since it only consists of four amino acids joined by peptide bonds. Many tetrapeptides are pharmacologically active, often showing affinity and specificity for a variety of receptors in protein-protein signaling. Present in nature are both linear and cyclic tetrapeptides (CTPs), the latter of which mimics protein reverse turns which are often present on the surface of proteins and druggable targets. Tetrapeptides may be cyclized by a fourth peptide bond or other covalent bonds.

<span class="mw-page-title-main">Ambrisentan</span> Chemical compound

Ambrisentan, sold under the brand name Letairis among others, is a drug used for the treatment of pulmonary hypertension. It is an endothelin receptor antagonist.

Big dynorphin is an endogenous opioid peptide of the dynorphin family that is composed of both dynorphin A and dynorphin B. Big dynorphin has the amino acid sequence: Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys-Trp-Asp-Asn-Gln-Lys-Arg-Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr. It has nociceptive and anxiolytic-like properties, as well as effects on memory in mice.

<span class="mw-page-title-main">Endothelin receptor type B</span> Protein-coding gene in the species Homo sapiens

Endothelin receptor type B, (ET-B) is a protein that in humans is encoded by the EDNRB gene.

<span class="mw-page-title-main">Spinorphin</span> Chemical compound

Spinorphin is an endogenous, non-classical opioid peptide of the hemorphin family first isolated from the bovine spinal cord (hence the prefix spin-) and acts as a regulator of the enkephalinases, a class of enzymes that break down endogenous the enkephalin peptides. It does so by inhibiting the enzymes aminopeptidase N (APN), dipeptidyl peptidase III (DPP3), angiotensin-converting enzyme (ACE), and neutral endopeptidase (NEP). Spinorphin is a heptapeptide and has the amino acid sequence Leu-Val-Val-Tyr-Pro-Trp-Thr (LVVYPWT). It has been observed to possess antinociceptive, antiallodynic, and anti-inflammatory properties. The mechanism of action of spinorphin has not been fully elucidated (i.e., how it acts to inhibit the enkephalinases), but it has been found to act as an antagonist of the P2X3 receptor, and as a weak partial agonist/antagonist of the FP1 receptor.

Leumorphin, also known as dynorphin B1–29, is a naturally occurring endogenous opioid peptide. Derived as a proteolytic cleavage product of residues 226-254 of prodynorphin, leumorphin is a nonacosapeptide and has the sequence Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Gln-Phe-Lys-Val-Val-Thr-Arg-Ser-Gln-Glu-Asp-Pro-Asn-Ala-Tyr-Ser-Gly-Glu-Leu-Phe-Asp-Ala. It can be further reduced to dynorphin B and dynorphin B-14 by pitrilysin metallopeptidase 1, an enzyme of the endopeptidase family. Leumorphin behaves as a potent and selective κ-opioid receptor agonist, similarly to other endogenous opioid peptide derivatives of prodynorphin.

Deltorphin, also known as deltorphin A and dermenkephalin, is a naturally occurring, exogenous opioid heptapeptide and thus, exorphin, with the amino acid sequence Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2. Along with the other deltorphins (such as deltorphin I and deltorphin II) and the dermorphins, deltorphin is endogenous to frogs of the genus Phyllomedusa such as P. bicolor and P. sauvagei where it is produced in their skin, and is not known to occur naturally in any other species. Deltorphin is one of the highest affinity and most selective naturally occurring opioid peptides known, acting as a very potent and highly specific agonist of the δ-opioid receptor.

<span class="mw-page-title-main">Macitentan</span> Chemical compound

Macitentan, sold under the brand name Opsumit, is an endothelin receptor antagonist (ERA) developed by Actelion and approved for the treatment of pulmonary arterial hypertension (PAH). The other two ERAs marketed as of 2014 are bosentan and ambrisentan. Macitentan is a dual ERA, meaning that it acts as an antagonist of two endothelin (ET) receptor subtypes, ETA and ETB. However, macitentan has a 50-fold increased selectivity for the ETA subtype compared to the ETB subtype. The drug received approval from the U.S. Food and Drug Administration (FDA) on 13 October 2013.

Centruroides suffusus suffusus toxin II (CssII) is a scorpion β-toxin from the venom of the scorpion Centruroides suffusus suffusus. CssII primarily affects voltage-gated sodium channels by causing a hyperpolarizing shift of voltage dependence, a reduction in peak transient current, and the occurrence of resurgent currents.

Kitasatospora misakiensis is a bacterium species from the genus of Kitasatospora which has been isolated from soil in Japan. Kitasatospora misakiensis produces tubermycin A, tubermycin B, misakimycin and the endothelin receptor antagonist BE-18257B.

<span class="mw-page-title-main">Sarafotoxin</span> Protein toxin family

Sarafotoxins (SRTXs) are a group of toxins present in the venom of Atractaspis engaddensis, and in clinical trials cause similar symptoms to patients diagnosed with acute giardiasis. Their etymology is from the name of the snake "שרף עין גדי" in Hebrew, pronounced "Saraf Ein Gedi". Together with endothelins (ETs), they form a homogenous family of strong vasoconstrictor isopeptides. Among them, a few slightly different substances can be named as SRTX-a, SRTX-b, SRTX-c, which were initially derived from A. engaddensis. Each one contains twenty-one amino acid residues that spontaneously fold into a defined tertiary structure, with two interchain-cysteine linkages and a long hydrophobic tail. There are also other compounds, however, they are mostly derivations of previously mentioned ones. The main differences in the family of endothelin and sarafotoxins appear at N-terminal of peptides, as C-terminal in all of them is almost the same.

<span class="mw-page-title-main">Bulevirtide</span> Antiviral medication

Bulevirtide, sold under the brand name Hepcludex, is an antiviral medication for the treatment of chronic hepatitis D.

DKK-SP1 is one of the many neurotoxins present in the scorpion Mesobuthus martensii. This toxin inhibits the voltage-gated sodium channel Nav1.8.

References

  1. 1 2 BQ-123 at Sigma-Aldrich
  2. ↑ Ihara M, Fukuroda T, Saeki T, Nishikibe M, Kojiri K, Suda H, Yano M (July 1991). "An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis". Biochemical and Biophysical Research Communications. 178 (1): 132–7. doi:10.1016/0006-291X(91)91789-F. PMID   1648907.
  3. ↑ Atkinson RA, Pelton JT (January 1992). "Conformational study of cyclo[D-Trp-D-Asp-Pro-D-Val-Leu], an endothelin-A receptor-selective antagonist". FEBS Letters. 296 (1): 1–6. doi: 10.1016/0014-5793(92)80390-3 . PMID   1309703.
  4. ↑ Krystek SR, Bassolino DA, Bruccoleri RE, Hunt JT, Porubcan MA, Wandler CF, Andersen NH (March 1992). "Solution conformation of a cyclic pentapeptide endothelin antagonist. Comparison of structures obtained from constrained dynamics and conformational search". FEBS Letters. 299 (3): 255–61. doi: 10.1016/0014-5793(92)80127-3 . PMID   1544503.
  5. ↑ Gonnella NC, Zhang X, Jin Y, Prakash O, Paris CG, Kolossváry I, et al. (May 1994). "Solvent effects on the conformation of cyclo(-D-Trp-D-Asp-Pro-D-Val-Leu-). An NMR spectroscopy and molecular modeling study". International Journal of Peptide and Protein Research. 43 (5): 454–62. doi:10.1111/j.1399-3011.1994.tb00544.x. PMID   8070969.
  6. ↑ Bean JW, Peishoff CE, Kopple KD (September 1994). "Conformations of cyclic pentapeptide endothelin receptor antagonists". International Journal of Peptide and Protein Research. 44 (3): 223–32. doi:10.1111/j.1399-3011.1994.tb00164.x. PMID   7822098.
  7. ↑ Ngoka LC, Gross ML (February 2000). "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 of Mass Spectrometry. 35 (2): 265–76. Bibcode:2000JMSp...35..265N. doi:10.1002/(SICI)1096-9888(200002)35:2<265::AID-JMS946>3.0.CO;2-#. PMID   10679990.
  8. ↑ Ngoka LC, Gross ML (January 1999). "Novel sodium binding properties of some cyclopentapeptide endothelin A selective receptor antagonists: electrospray and fast-atom-bombardment mass spectrometric studies". Biochemical and Biophysical Research Communications. 254 (3): 713–9. doi:10.1006/bbrc.1998.9772. PMID   9920807.
  9. ↑ Büyükgebiz O, Aktan AO, Haklar G, Yalçin AS, Yeğen C, Yalin R, Ercan ZS (1996). "BQ-123, a specific endothelin (ETA) receptor antagonist, prevents ischemia-reperfusion injury in kidney transplantation". Transplant International. 9 (3): 201–7. doi:10.1007/BF00335386. PMID   8723187. S2CID   39612393.
  10. ↑ Clozel M, Watanabe H (1993). "BQ-123, a peptidic endothelin ETA receptor antagonist, prevents the early cerebral vasospasm following subarachnoid hemorrhage after intracisternal but not intravenous injection". Life Sciences. 52 (9): 825–34. doi:10.1016/0024-3205(93)90081-d. PMID   8437512.
  11. ↑ Clavell AL, Stingo AJ, Margulies KB, Brandt RR, Burnett JC (March 1995). "Role of endothelin receptor subtypes in the in vivo regulation of renal function". The American Journal of Physiology. 268 (3 Pt 2): F455-60. doi:10.1152/ajprenal.1995.268.3.F455. PMID   7900845.
  12. ↑ Gellai M, Jugus M, Fletcher T, DeWolf R, Nambi P (February 1994). "Reversal of postischemic acute renal failure with a selective endothelinA receptor antagonist in the rat". The Journal of Clinical Investigation. 93 (2): 900–6. doi:10.1172/JCI117046. PMC   293964 . PMID   8113422.
  13. ↑ Mino N, Kobayashi M, Nakajima A, Amano H, Shimamoto K, Ishikawa K, et al. (October 1992). "Protective effect of a selective endothelin receptor antagonist, BQ-123, in ischemic acute renal failure in rats". European Journal of Pharmacology. 221 (1): 77–83. doi:10.1016/0014-2999(92)90774-x. PMID   1459192.
  14. ↑ Ishikawa K, Fukami T, Nagase T, Fujita K, Hayama T, Niiyama K, et al. (May 1992). "Cyclic pentapeptide endothelin antagonists with high ETA selectivity. Potency- and solubility-enhancing modifications". Journal of Medicinal Chemistry. 35 (11): 2139–42. doi:10.1021/jm00089a028. PMID   1317926.
  15. ↑ Berrazueta JR, Bhagat K, Vallance P, MacAllister RJ (December 1997). "Dose- and time-dependency of the dilator effects of the endothelin antagonist, BQ-123, in the human forearm". British Journal of Clinical Pharmacology. 44 (6): 569–71. doi:10.1046/j.1365-2125.1997.t01-1-00631.x. PMC   2042881 . PMID   9431833.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.