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Title 

Structure-antagonistic activity relationships of an NK-2 tachykinin receptor antagonist, L-659,877 and its analogues

Authors 

Jong Myung HaSong Yub ShinHea Nam HongDuk Joon SuhTae Sik JangShin Won KangSun Jin KueanBae Jin Ha

Publisher 

Springer Verlag (Germany)

Issue Date 

1996

Citation 

Journal of Biochemistry and Molecular Biology, vol. 29, no. 5, pp. 429-435

Keywords 

antagonistcyclic hexapeptideguinea pig tracheaL-659,877Neurokinin-2 (NK-2)

Abstract 

To investigate the structure-antagonistic relationship of the cyclohexapeptide L-659,877, a selective NK-2 tachykinin receptor antagonist, seven analogues were chemically synthesized by a solid phase method. The agonistic and antagonistic activities of the analogues were evaluated by contraction assay using the smooth muscle of guinea pig trachea (GPT) containing the NK-2 receptor. It was shown that the aromatic ring of Phe at position 3 and the sulfur group of Met at position 6 in L-659,877 were essential for binding to the NK-2 receptor. Decrease in antagonistic activity of L-659,877 caused by substituting Leu for Nle at position 5 indicates that the γ methyl group and side chain length of Leu plays an important role in its antagonistic action. Although the activity was slightly lower than L-659,877, cyclo [βAla8]NKA(4-10) (analogue 1) showed potential antagonistic activity for the NK-2 receptor. It was confirmed that the expansion of the ring in L-659,877 by substitution of βAla for Gly at position 4 stabilized its conformation monitored by CD spectra. The results suggest that analogue 1 can be used as a new leader compound to design a more powerful, selective, and stable NK-2 receptor antagonist.

ISSN 

1225-8687

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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