[NMR paper] Targeting the Endocannabinoid System for Neuroprotection: A (19)F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.
Targeting the Endocannabinoid System for Neuroprotection: A (19)F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.
Related ArticlesTargeting the Endocannabinoid System for Neuroprotection: A (19)F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.
J Pharm Pharmacol (Los Angel). 2013;1(1)
Authors: Zhuang J, Yang DP, Tian X, Nikas SP, Sharma R, Guo JJ, Makriyannis A
Abstract
Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection. We have developed a brain permeable FAAH inhibitor, AM5206, which has served as a valuable pharmacological tool to explore neuroprotective effects of this class of compounds. In the present work, we characterized the interactions of AM5206 with a representative AEA carrier protein, human serum albumin (HSA), using (19)F nuclear magnetic resonance (NMR) spectroscopy. Our data showed that as a drug carrier, albumin can significantly enhance the solubility of AM5206 in aqueous environment. Through a series of titration and competitive binding experiments, we also identified that AM5206 primarily binds to two distinct sites within HSA. Our results may provide insight into the mechanism of HSA-AM5206 interactions. The findings should also help in the development of suitable formulations of the lipophilic AM5206 and its congeners for their effective delivery to specific target sites in the brain.
PMID: 24533425 [PubMed - as supplied by publisher]
Dynamic Nuclear Polarization Study of Inhibitor Binding to the M218-60 Proton Transporter from Influenza A
From the The DNP-NMR Blog:
Dynamic Nuclear Polarization Study of Inhibitor Binding to the M218-60 Proton Transporter from Influenza A
Andreas, L.B., et al., Dynamic Nuclear Polarization Study of Inhibitor Binding to the M218-60 Proton Transporter from Influenza A. Biochemistry, 2013.
http://www.ncbi.nlm.nih.gov/pubmed/23480101
nmrlearner
News from NMR blogs
0
04-15-2013 08:52 AM
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
NMR structure and dynamics of recombinant wild type and mutated jerdostatin, a selective inhibitor of integrin ?(1) ?(1).
Proteins. 2011 May 10;
Authors: Carbajo RJ, Sanz L, Mosulén S, Pérez A, Marcinkiewicz C, Pineda-Lucena A, Calvete JJ
NMR analysis of four recombinant jerdostatin molecules was assessed to define the structural basis of two naturally occurring gain-of-function events: C-terminal dipeptide processing and...
nmrlearner
Journal club
0
06-10-2011 11:52 AM
[NMR paper] Selective inhibition of Src SH2 by a novel thiol-targeting tricarbonyl-modified inhib
Selective inhibition of Src SH2 by a novel thiol-targeting tricarbonyl-modified inhibitor and mechanistic analysis by (1)H/(13)C NMR spectroscopy.
Related Articles Selective inhibition of Src SH2 by a novel thiol-targeting tricarbonyl-modified inhibitor and mechanistic analysis by (1)H/(13)C NMR spectroscopy.
Bioorg Med Chem Lett. 2001 Jul 9;11(13):1665-9
Authors: Sundaramoorthi R, Siedem C, Vu CB, Dalgarno DC, Laird EC, Botfield MC, Combs AB, Adams SE, Yuan RW, Weigele M, Narula SS
Detailed analysis of Src SH2 binding by peptides containing a...
nmrlearner
Journal club
0
11-19-2010 08:44 PM
[NMR paper] NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: cha
NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: changes in the (1)H, (13)C and (15)N NMR chemical shifts of turkey ovomucoid third domain upon binding to bovine chymotrypsin A(alpha).
Related Articles NMR chemical shift mapping of the binding site of a protein proteinase inhibitor: changes in the (1)H, (13)C and (15)N NMR chemical shifts of turkey ovomucoid third domain upon binding to bovine chymotrypsin A(alpha).
J Mol Recognit. 2001 May-Jun;14(3):166-71
Authors: Song J, Markley JL
The substrate-like...
nmrlearner
Journal club
0
11-19-2010 08:32 PM
[NMR paper] Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) sympor
Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) symport protein GalP, of Escherichia coli.
Related Articles Selective NMR observation of inhibitor and sugar binding to the galactose-H(+) symport protein GalP, of Escherichia coli.
Biochim Biophys Acta. 2000 Dec 20;1509(1-2):55-64
Authors: Appleyard AN, Herbert RB, Henderson PJ, Watts A, Spooner PJ
The binding of the transport inhibitor forskolin, synthetically labelled with (13)C, to the galactose-H(+) symport protein GalP, overexpressed in its native inner...
nmrlearner
Journal club
0
11-19-2010 08:29 PM
Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.
Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.
Related Articles Discovery of a potent and selective Bcl-2 inhibitor using SAR by NMR.
Bioorg Med Chem Lett. 2010 Sep 15;
Authors: Petros AM, Huth JR, Oost T, Park CM, Ding H, Wang X, Zhang H, Nimmer P, Mendoza R, Sun C, Mack J, Walter K, Dorwin S, Gramling E, Ladror U, Rosenberg SH, Elmore SW, Fesik SW, Hajduk PJ
The Bcl-2 family of proteins plays a major role in the regulation of apoptosis, or programmed cell death. Overexpression of the anti-apoptotic members of this...
nmrlearner
Journal club
0
09-29-2010 08:04 AM
[NMR paper] The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and
The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and fluorescence spectroscopic determination.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and fluorescence spectroscopic determination.
Biochemistry. 1997 Feb 18;36(7):1719-29
Authors: Stolowich NJ, Frolov A, Atshaves B, Murphy EJ, Jolly CA, Billheimer JT, Scott AI, Schroeder F
The interaction and orientation of fatty acids...
nmrlearner
Journal club
0
08-22-2010 03:31 PM
[NMR paper] The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and
The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and fluorescence spectroscopic determination.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.acs.org-images-acspubs.jpg Related Articles The sterol carrier protein-2 fatty acid binding site: an NMR, circular dichroic, and fluorescence spectroscopic determination.
Biochemistry. 1997 Feb 18;36(7):1719-29
Authors: Stolowich NJ, Frolov A, Atshaves B, Murphy EJ, Jolly CA, Billheimer JT, Scott AI, Schroeder F
The interaction and orientation of fatty acids...
Targeting the Endocannabinoid System for Neuroprotection: A (19)F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.
Linear Mode
