Aladan scanning: The structure-activity relationship of dynorphin A

• 来源期刊: 中国科学B辑（英文版）
• 年，卷（期）: 2009,（3）
• 页码范围: 338-343
• 页数: 6页
• 语种: 英文
• DOI: 10.1007/s11426-008-0150-0

摘要

An unnatural amino acid, β-[6'-(N, N-dimethyl)amino-2'-naphthoyl]alanine (Ald) showing polarity-sen sitive fluorescence characteristics, was synthesized. A thorough Aid-scan of dynorphin A (Dyn A), the putative endogenous ligand for κ opioid receptors, was then performed. Replacement of the amino acid residues in positions 5, 8, 10, 12 or 14 of Dyn A(1-13)-NH2 with Ald resulted in compounds that had almost equal κ binding affinity compared with that of the parent compound; on the other hand, substi-tution of residues in position 1 or 4 with Aid decreased x-receptor binding affinity. These results indi-cate that Tyr and Phe in Dyn A are very important for maintaining its κ-opioid activity. Evidence from receptor binding assay clearly displays that [Ald5]Dyn A(1-13)-NH2 is a highly selective κ-opioid re-ceptor agonist. An evaluation of the interaction of Aid-containing Dyn A(1-13)-NH2 analogues with SDS and DPC micelles was also performed. Interestingly, [Ald1]Dyn A(1-13)-NH2 and [Ald4]Dyn A(1-13)-NH2 showed quite different fluorescence emission maxima in SDS and DPC micelles. This indicates that both peptides are sensitive to electronic properties of the polar surface of the micelles.