Octreotide-micelle interactions via NMR spectroscopy

• Main Authors: Jheng-You Chen, 陳政佑
• Other Authors: Wei-Jyun Chian
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/68203698846272456506

碩士 === 朝陽科技大學 === 應用化學系碩士班 === 97 === This paper studies a conformational of an octapeptide D-Phe1-cyclo[Cys2-Phe3-D-Trp4-Lys5-Thr6-Cys7]-Thr8-ol (disulfide bridged), known as Octreotide (or SMS 201-995 or sandostatin) using nuclear magnetic resonance spectroscopy and molecular modeling method. Octreotide displays both somatostatin-like and opioid-like bioactivities which colud be mediated through trans-membrane receptors SSTRs. Predominant selectivity to SSTR2、SSTR3、SSTR5 located in brain, hypothalamus and pituitary has been identified for Octreotide. The interaction between Octreotide and SDS micelle is also monitored by the blue shift and attenuation of fluorescence signal of peptide upon the introduction of micelle. The association constant of Octreotide-micelle complex is estimated by a two-state approximation based on the diffusion coefficients, measured by PFG-NMR spectroscopy, for Octreotide in aqueous and micellar solutions, respectively. The binding constant is about 6.12×102 M-1. These results are evidences to show that the tryptophan residue locates in the hydrophobic environment of the micelle and the which are consistent with the observation in NMR experiments. Base on the analysis of chemical shift deviation, NOE cross-peaks and coupling constants, the backbone conformation of Octreotide, under micellar environment, was in equilibrium between β-strand and helix-like secondary structure fold, with a β-turn centered at D-Trp4-Lys5. The correlation between the relative positions of the aromatic side-chain of the peptide and its receptor affinity is further discussed.