PDBsum entry 2soc

Octreotide

PDB id: 2soc

Contents

Ligands

DPN-CYS-PHE-DTR-LYS-THR-CYS-THO

References listed in PDB file

Key reference

Title

Multiconformational nmr analysis of sandostatin (octreotide): equilibrium between beta-Sheet and partially helical structures.

Authors

G.Melacini, Q.Zhu, M.Goodman.

Ref.

Biochemistry, 1997, 36, 1233-1241. [DOI no: 10.1021/bi962497o]

PubMed id

9063871

Abstract

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.

Secondary reference #1

Title

Structure of octreotide, A somatostatin analogue.

Authors

E.Pohl, A.Heine, G.M.Sheldrick, Z.Dauter, K.S.Wilson, J.Kallen, W.Huber, P.J.Pfäffli.

Ref.

Acta Crystallogr D Biol Crystallogr, 1995, 51, 48-59. [DOI no: 10.1107/S0907444994006104]

PubMed id

15299335

Figure 5.
Fig. 5. Superposition of the 20 ring atoms of molecules II and HI.

Figure 8.
Fig. 8. Space-filling plots of the three independent peptide molecules.

The above figures are reproduced from the cited reference with permission from the IUCr