PDBsum entry 2soc

Octreotide

PDB id: 2soc

Contents

Ligands

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

PDB id:

2soc

Name:

Octreotide

Title:

Nmr study of the backbone conformational equilibria of sandostatin, two representative minimum energy partially helical structures

Structure:

Sandostatin. Chain: a. Synonym: octreotide. Engineered: yes

Source:

not given

NMR struc:

2 models

Authors:

G.Melacini,Q.Zhu,M.Goodman

Key ref:

G.Melacini et al. (1997). Multiconformational NMR analysis of sandostatin (octreotide): equilibrium between beta-sheet and partially helical structures. Biochemistry, 36, 1233-1241. PubMed id: 9063871 DOI: 10.1021/bi962497o

Date:

26-Nov-96 Release date: 21-Apr-97

DOI no: 10.1021/bi962497o

Biochemistry 36:1233-1241 (1997)

PubMed id: 9063871

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

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

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.