کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1363249 | 981507 | 2007 | 6 صفحه PDF | دانلود رایگان |
Endogenous opioid peptides consist of a conserved amino acid residue of Phe3 and Phe4, although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the μ opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe3 and Phe4 in binding to the μ receptor, we synthesized a series of analogs in which Phe3 and Phe4 were replaced by various amino acids. It was found that the aromaticity of the Phe-β-phenyl groups of Phe3 and Phe4 is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe3 and Phe4 of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp3]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses.
Endomorphin-2 is a unique opioid peptide possessing the two Phe residues at positions 3 and 4. It was evidenced these residues provide the receptor binding abilities with different interaction profiles.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 15, Issue 11, 1 June 2007, Pages 3883–3888