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2soc
From Proteopedia
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NMR STUDY OF THE BACKBONE CONFORMATIONAL EQUILIBRIA OF SANDOSTATIN, TWO REPRESENTATIVE MINIMUM ENERGY PARTIALLY HELICAL STRUCTURES
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
2SOC 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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