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1soc
From Proteopedia
(New page: 200px<br /><applet load="1soc" size="450" color="white" frame="true" align="right" spinBox="true" caption="1soc" /> '''NMR STUDY OF THE BACKBONE CONFORMATIONAL EQU...) |
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| - | [[Image:1soc.gif|left|200px]]<br /><applet load="1soc" size=" | + | [[Image:1soc.gif|left|200px]]<br /><applet load="1soc" size="350" color="white" frame="true" align="right" spinBox="true" |
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'''NMR STUDY OF THE BACKBONE CONFORMATIONAL EQUILIBRIA OF SANDOSTATIN, MINIMIZED AVERAGE BETA-SHEET STRUCTURE'''<br /> | '''NMR STUDY OF THE BACKBONE CONFORMATIONAL EQUILIBRIA OF SANDOSTATIN, MINIMIZED AVERAGE BETA-SHEET STRUCTURE'''<br /> | ||
==Overview== | ==Overview== | ||
| - | This paper reports a detailed conformational analysis by 1H NMR (DMSO-d6, 300 K) and molecular modeling of the octapeptide | + | This paper reports a detailed conformational analysis by 1H NMR (DMSO-d6, 300 K) and molecular modeling of the octapeptide D-Phe1-Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7+ ++-Thr8-ol (disulfide bridged) known as sandostatin (or SMS 201-995 or octreotide) with both somatostatin-like and opioid-like bioactivities. This is the initial report on sandostatin showing that attempts to explain all NMR data using a single average conformation reveal several important inconsistencies including severe violations of mutually exclusive backbone-to-backbone NOEs. The inconsistencies are solved by assuming an equilibrium between antiparallel beta-sheet structures and conformations in which the C-terminal residues form a 3(10) helix-like fold (helical ensemble). This conformational equilibrium is consistent with previous X-ray diffraction investigations which show that sandostatin can adopt both the beta-sheet and the 3(10) helix-like secondary structure folds. In addition, indications of a conformational equilibrium between beta-sheet and helical structures are also found in solvent systems different from DMSO-d6 and for other highly bioactive analogs of sandostatin. In these cases a proper multiconformational NMR refinement is important in order to avoid conformational averaging artifacts. Finally, using the known models for somatostatin-like and opioid-like bioactivities of sandostatin analogs, the present investigation shows the potentials of the proposed structures for the design of novel sandostatin-based conformationally restricted peptidomimetics. These analogs are expected to refine the pharmacophore models for sandostatin bioactivities. |
==About this Structure== | ==About this Structure== | ||
| - | 1SOC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http:// | + | 1SOC is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1SOC OCA]. |
==Reference== | ==Reference== | ||
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[[Category: sandostatin]] | [[Category: sandostatin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:03:35 2008'' |
Revision as of 13:03, 21 February 2008
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NMR STUDY OF THE BACKBONE CONFORMATIONAL EQUILIBRIA OF SANDOSTATIN, MINIMIZED AVERAGE BETA-SHEET STRUCTURE
Overview
This paper reports a detailed conformational analysis by 1H NMR (DMSO-d6, 300 K) and molecular modeling of the octapeptide D-Phe1-Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7+ ++-Thr8-ol (disulfide bridged) known as sandostatin (or SMS 201-995 or octreotide) with both somatostatin-like and opioid-like bioactivities. This is the initial report on sandostatin showing that attempts to explain all NMR data using a single average conformation reveal several important inconsistencies including severe violations of mutually exclusive backbone-to-backbone NOEs. The inconsistencies are solved by assuming an equilibrium between antiparallel beta-sheet structures and conformations in which the C-terminal residues form a 3(10) helix-like fold (helical ensemble). This conformational equilibrium is consistent with previous X-ray diffraction investigations which show that sandostatin can adopt both the beta-sheet and the 3(10) helix-like secondary structure folds. In addition, indications of a conformational equilibrium between beta-sheet and helical structures are also found in solvent systems different from DMSO-d6 and for other highly bioactive analogs of sandostatin. In these cases a proper multiconformational NMR refinement is important in order to avoid conformational averaging artifacts. Finally, using the known models for somatostatin-like and opioid-like bioactivities of sandostatin analogs, the present investigation shows the potentials of the proposed structures for the design of novel sandostatin-based conformationally restricted peptidomimetics. These analogs are expected to refine the pharmacophore models for sandostatin bioactivities.
About this Structure
1SOC is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Multiconformational NMR analysis of sandostatin (octreotide): equilibrium between beta-sheet and partially helical structures., Melacini G, Zhu Q, Goodman M, Biochemistry. 1997 Feb 11;36(6):1233-41. PMID:9063871
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