Literature DB >> 22029276

p-(4-Azipentyl)propofol: a potent photoreactive general anesthetic derivative of propofol.

Deirdre S Stewart1, Pavel Y Savechenkov, Zuzana Dostalova, David C Chiara, Rile Ge, Douglas E Raines, Jonathan B Cohen, Stuart A Forman, Karol S Bruzik, Keith W Miller.   

Abstract

We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA(A) receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABA(A) receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus, p-4-AziC5-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites.

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Year:  2011        PMID： 22029276      PMCID： PMC3580944          DOI： 10.1021/jm200943f

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  34 in total

1.  Identification and characterization of membrane-associated polypeptides in Torpedo nicotinic acetylcholine receptor-rich membranes by hydrophobic photolabeling.

Authors:  M P Blanton; A K Lala; J B Cohen
Journal:  Biochim Biophys Acta       Date:  2001-06-06

2.  Efficient synthesis of 3-trifluoromethylphenyldiazirinyl oleic acid derivatives and their biological activity for protein kinase C.

Authors:  Makoto Hashimoto; Kensuke Nabeta; Kentaro Murakami
Journal:  Bioorg Med Chem Lett       Date:  2003-05-05       Impact factor: 2.823

3.  X-ray structures of general anaesthetics bound to a pentameric ligand-gated ion channel.

Authors:  Hugues Nury; Catherine Van Renterghem; Yun Weng; Alphonso Tran; Marc Baaden; Virginie Dufresne; Jean-Pierre Changeux; James M Sonner; Marc Delarue; Pierre-Jean Corringer
Journal:  Nature       Date:  2011-01-20       Impact factor: 49.962

4.  Mapping the agonist binding site of the nicotinic acetylcholine receptor. Orientation requirements for activation by covalent agonist.

Authors:  D A Sullivan; J B Cohen
Journal:  J Biol Chem       Date:  2000-04-28       Impact factor: 5.157

5.  Methionine 286 in transmembrane domain 3 of the GABAA receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics.

Authors:  M D Krasowski; K Nishikawa; N Nikolaeva; A Lin; N L Harrison
Journal:  Neuropharmacology       Date:  2001-12       Impact factor: 5.250

6.  General anesthetic potencies of a series of propofol analogs correlate with potency for potentiation of gamma-aminobutyric acid (GABA) current at the GABA(A) receptor but not with lipid solubility.

Authors:  M D Krasowski; A Jenkins; P Flood; A Y Kung; A J Hopfinger; N L Harrison
Journal:  J Pharmacol Exp Ther       Date:  2001-04       Impact factor: 4.030

7.  4D-QSAR analysis of a set of propofol analogues: mapping binding sites for an anesthetic phenol on the GABA(A) receptor.

Authors:  Matthew D Krasowski; Xuan Hong; A J Hopfinger; Neil L Harrison
Journal:  J Med Chem       Date:  2002-07-18       Impact factor: 7.446

8.  Identification of binding sites in the nicotinic acetylcholine receptor for [3H]azietomidate, a photoactivatable general anesthetic.

Authors:  Michael R Ziebell; Selvanayagam Nirthanan; S Shaukat Husain; Keith W Miller; Jonathan B Cohen
Journal:  J Biol Chem       Date:  2004-02-03       Impact factor: 5.157

9.  Gating allosterism at a single class of etomidate sites on alpha1beta2gamma2L GABA A receptors accounts for both direct activation and agonist modulation.

Authors:  Dirk Rüsch; Huijun Zhong; Stuart A Forman
Journal:  J Biol Chem       Date:  2004-03-11       Impact factor: 5.157

10.  The in vitro and in vivo enantioselectivity of etomidate implicates the GABAA receptor in general anaesthesia.

Authors:  Delia Belelli; Anna-Lisa Muntoni; Simon D Merrywest; Luc J Gentet; Anna Casula; Helen Callachan; Paola Madau; David K Gemmell; Niall M Hamilton; Jeremy J Lambert; Keith T Sillar; John A Peters
Journal:  Neuropharmacology       Date:  2003-07       Impact factor: 5.250
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  22 in total

1.  Allyl m-trifluoromethyldiazirine mephobarbital: an unusually potent enantioselective and photoreactive barbiturate general anesthetic.

Authors:  Pavel Y Savechenkov; Xi Zhang; David C Chiara; Deirdre S Stewart; Rile Ge; Xiaojuan Zhou; Douglas E Raines; Jonathan B Cohen; Stuart A Forman; Keith W Miller; Karol S Bruzik
Journal:  J Med Chem       Date:  2012-07-17       Impact factor: 7.446

2.  Propofol inhibits SIRT2 deacetylase through a conformation-specific, allosteric site.

Authors:  Brian P Weiser; Roderic G Eckenhoff
Journal:  J Biol Chem       Date:  2015-02-09       Impact factor: 5.157

Review 3.  Mapping General Anesthetic Sites in Heteromeric γ-Aminobutyric Acid Type A Receptors Reveals a Potential For Targeting Receptor Subtypes.

Authors:  Stuart A Forman; Keith W Miller
Journal:  Anesth Analg       Date:  2016-11       Impact factor: 5.108

4.  Mechanisms revealed through general anesthetic photolabeling.

Authors:  Brian P Weiser; Kellie A Woll; William P Dailey; Roderic G Eckenhoff
Journal:  Curr Anesthesiol Rep       Date:  2014-03-01

5.  Common general anesthetic propofol impairs kinesin processivity.

Authors:  Brandon M Bensel; Stephanie Guzik-Lendrum; Erin M Masucci; Kellie A Woll; Roderic G Eckenhoff; Susan P Gilbert
Journal:  Proc Natl Acad Sci U S A       Date:  2017-05-08       Impact factor: 11.205

6.  A potent photoreactive general anesthetic with novel binding site selectivity for GABAA receptors.

Authors:  Abdelrahman R Shalabi; Zhiyi Yu; Xiaojuan Zhou; Youssef Jounaidi; Hanwen Chen; Jiajia Dai; Daniel E Kent; Hua-Jun Feng; Stuart A Forman; Jonathan B Cohen; Karol S Bruzik; Keith W Miller
Journal:  Eur J Med Chem       Date:  2020-03-23       Impact factor: 6.514

7.  Direct modulation of microtubule stability contributes to anthracene general anesthesia.

Authors:  Daniel J Emerson; Brian P Weiser; John Psonis; Zhengzheng Liao; Olena Taratula; Ashley Fiamengo; Xiaozhao Wang; Keizo Sugasawa; Amos B Smith; Roderic G Eckenhoff; Ivan J Dmochowski
Journal:  J Am Chem Soc       Date:  2013-03-29       Impact factor: 15.419

Review 8.  Shedding Light on Anesthetic Mechanisms: Application of Photoaffinity Ligands.

Authors:  Kellie A Woll; William P Dailey; Grace Brannigan; Roderic G Eckenhoff
Journal:  Anesth Analg       Date:  2016-11       Impact factor: 5.108

9.  Specificity of intersubunit general anesthetic-binding sites in the transmembrane domain of the human α1β3γ2 γ-aminobutyric acid type A (GABAA) receptor.

Authors:  David C Chiara; Selwyn S Jayakar; Xiaojuan Zhou; Xi Zhang; Pavel Y Savechenkov; Karol S Bruzik; Keith W Miller; Jonathan B Cohen
Journal:  J Biol Chem       Date:  2013-05-15       Impact factor: 5.157

10.  Azo-propofols: photochromic potentiators of GABA(A) receptors.

Authors:  Marco Stein; Simon J Middendorp; Valentina Carta; Ervin Pejo; Douglas E Raines; Stuart A Forman; Erwin Sigel; Dirk Trauner
Journal:  Angew Chem Int Ed Engl       Date:  2012-09-11       Impact factor: 15.336
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