Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Conjugates of Enkephalin Analogs: Synthesis and Discrimination of μ and δ Opioid Receptors Based on Membrane Compartment Concept

  • Hong, Nam-Joo (School of Biotechnology, Yeungnam University) ;
  • Jin, Dong-Hoon (Department of Anatomy and Tumor Immunity Medical Research Center, College of Medicine, Seoul National University) ;
  • Hong, Eun-Young (School of Chemical and Biological Engineering, Seoul National University)
  • Published : 2009.03.20
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Abstract

A series of conjugated cyclic and linear enkephalin analogs, Tyr-c[D-A2bu-Gly-Phe-Asp(NH-X)], where X = methyl, stearyl or$ PEG_350$, and Tyr-D-Ala-Gly-Phe-Cys(S-X), where X = methyl, octyl, or farnesyl, were synthesized in solution to investigate the receptor selectivity of opioids based on Schwyzer's membrane compartment $concepts.^{5,6}$ Cyclizations of the target compounds were achieved in high yields (> 60%) employing BOP, $NaHCO_3$ in DMF despite the steric hindrance of the bulky pendant groups. In the binding assay, the hydrophobic fatty acyl conjugates retained $\mu$-receptor selectivity. The unsaturated farnesyl conjugate exhibited the increased binding affinity than the saturated stearyl conjugate for both $\mu$-and $\delta$-opioid receptors. The PEG conjugates displayed the $\delta$-receptor selectivity. The low molecular weight $PEG_350$ conjugate exhibited the increase selectivity than the high molecular weight $PEG_5000$ conjugate to the $\delta$-receptor. The results of this study support the membrane compartment concepts.

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