Discovery of a potent and efficacious peptide derivative for ?/? opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.
Discovery of a potent and efficacious peptide derivative for ?/? opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.
Discovery of a potent and efficacious peptide derivative for ?/? opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.
J Med Chem. 2011 Apr 14;54(7):2029-38
Authors: Yamamoto T, Nair P, Largent-Milnes TM, Jacobsen NE, Davis P, Ma SW, Yamamura HI, Vanderah TW, Porreca F, Lai J, Hruby VJ
Multivalent ligands with ?/? opioid agonist and NK1 antagonist activities have shown promising analgesic potency without detectable sign of toxicities, including motor skill impairment and opioid-induced tolerance. To improve their biological activities and metabolic stability, structural optimization was performed on our peptide-derived lead compounds by introducing 2',6'-dimethyl-L-tyrosine (Dmt) instead of Tyr at the first position. The compound 7 (Dmt-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)-Bzl]) showed improved multivalent bioactivities compared to those of the lead compounds, had more than 6 h half-life in rat plasma, and had significant antinociceptive efficacy in vivo. The NMR structural analysis suggested that Dmt(1) incorporation in compound 7 induces the structured conformation in the opioid pharmacophore (N-terminus) and simultaneously shifts the orientation of the NK1 pharmacophore (C-terminus), consistent with its affinities and activities at both opioid and NK1 receptors. These results indicate that compound 7 is a valuable research tool to seek a novel analgesic drug.
Transferred NOESY NMR studies of biotin mimetic peptide (FSHPQNT) bound to streptavidin: A structural model for studies of peptide-protein interactions.
Transferred NOESY NMR studies of biotin mimetic peptide (FSHPQNT) bound to streptavidin: A structural model for studies of peptide-protein interactions.
Transferred NOESY NMR studies of biotin mimetic peptide (FSHPQNT) bound to streptavidin: A structural model for studies of peptide-protein interactions.
Chem Biol Drug Des. 2011 Feb 5;
Authors: Gizachew D, Dratz E
Protein-protein interactions control signaling, specific adhesion and many other biological functions. The three dimensional structures of the interfaces and bound ligand can be...
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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...
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09-29-2010 08:04 AM
[BMNRC community] NMR-based screening: a powerful tool in fragment-based drug discovery
NMR-based screening: a powerful tool in fragment-based drug discovery
http://www.rsc.org/delivery/_ArticleLinking/DisplayHTMLArticleforfree.cfm?JournalCode=AN&Year=2007&ManuscriptID=b709658p&Iss=7
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09-02-2010 04:59 AM
[NMR paper] NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.nrc-cnrc.gc.ca-cisti-journals-rp-gifs-PubMed_logo_e.gif Related Articles NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
Biochem Cell Biol. 1997;75(2):163-9
Authors: Brockbank RL, Vogel HJ
The proton and carbon-13 NMR resonances for the 13-residue synthetic RRsrc peptide were completely assigned using two-dimensional NMR spectroscopy. This peptide contains a tyrosine in position 9 that can be phosphorylated...
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08-22-2010 03:31 PM
[NMR paper] NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--pubs.nrc-cnrc.gc.ca-cisti-journals-rp-gifs-PubMed_logo_e.gif Related Articles NMR studies of the RRsrc peptide, a tyrosine kinase substrate.
Biochem Cell Biol. 1997;75(2):163-9
Authors: Brockbank RL, Vogel HJ
The proton and carbon-13 NMR resonances for the 13-residue synthetic RRsrc peptide were completely assigned using two-dimensional NMR spectroscopy. This peptide contains a tyrosine in position 9 that can be phosphorylated...
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08-22-2010 03:03 PM
[NMR paper] NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similari
NMR-based structural studies of the pNR-2/pS2 single domain trefoil peptide. Similarities to porcine spasmolytic peptide and evidence for a monomeric structure.
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Eur J Biochem. 1995 Nov 1;233(3):847-55
Authors: Polshakov VI, Frenkiel TA,...
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[NMR paper] Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determinati
Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments.
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J Antibiot (Tokyo). 1991 Feb;44(2):172-80
Authors: Wyss DF, Lahm HW, Manneberg M, Labhardt AM
Anantin, a naturally occurring peptide from Streptomyces coerulescens, binds competitively to the receptor of atrial natriuretic...
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08-21-2010 11:16 PM
[NMR paper] 13C and 15N NMR studies on the interaction between 6,7-dimethyl-8-ribityllumazine and
13C and 15N NMR studies on the interaction between 6,7-dimethyl-8-ribityllumazine and lumazine protein.
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Biochemistry. 1990 Feb 20;29(7):1823-8
Authors: Vervoort J, O'Kane DJ, Müller F, Bacher A, Strobl G, Lee J
The interaction between the prosthetic group 6,7-dimethyl-8-(1'-D-ribityl)lumazine and the lumazine apoproteins from two marine bioluminescent bacteria, one from a relatively thermophilic species, Photobacterium...
Discovery of a potent and efficacious peptide derivative for ?/? opioid agonist/neurokinin 1 antagonist activity with a 2',6'-dimethyl-L-tyrosine: in vitro, in vivo, and NMR-based structural studies.
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