Conjugates of Enkephalin Analogs: Synthesis and Discrimination of ¥ì and ¥ä Opioid Receptors Based on Membrane Compartment Concept

Bulletin of the Korean chemical society

Dong Hoon Jin¹  Eun Young Hong¹  Nam Joo Hong¹ 

关键词: Enkephalin;    Conjugate;    Membrane compartment;    Bioactivity;   

DOI  :  

学科分类：化学（综合）

来源: Korean Chemical Society

【 摘 要 】

A series of conjugated cyclic and linear enkephalin analogs, Tyr-c[D-A₂bu-Gly-Phe-Asp(NH-X)], where X = methyl, stearyl or PEG₃₅₀, 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, NaHCO₃ in DMF despite the steric hindrance of the bulky pendant groups. In the binding assay, the hydrophobic fatty acyl conjugates retained �?-receptor selectivity. The unsaturated farnesyl conjugate exhibited the increased binding affinity than the saturated stearyl conjugate for both �?-and �?-opioid receptors. The PEG conjugates displayed the �?-receptor selectivity. The low molecular weight PEG₃₅₀ conjugate exhibited the increase selectivity than the high molecular weight PEG₅₀₀₀ conjugate to the �?-receptor. The results of this study support the membrane compartment concepts.

【 授权许可】

Unknown