1186668-63-2Relevant academic research and scientific papers
A new class of highly potent and selective endomorphin-1 analogues containing α-methylene-β-aminopropanoic acids (map)
Wang, Yuan,Xing, Yanhong,Liu, Xin,Ji, Hong,Kai, Ming,Chen, Zongyao,Yu, Jing,Zhao, Depeng,Ren, Hui,Wang, Rui
supporting information; experimental part, p. 6224 - 6236 (2012/09/05)
A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural α-methylene-β-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the μ-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (Kiμ = 0.221 nM) and efficacy (EC 50 = 0.0334 nM, Emax = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the μ-opioid receptor.
