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

Cited 0 time in scopus
Metadata Downloads
Title
Structure-antagonistic activity relationships of an NK-2 tachykinin receptor antagonist, L-659,877 and its analogues
Author(s)
Jong Myung Ha; Song Yub Shin; Hea Nam Hong; Duk Joon Suh; Tae Sik Jang; Shin Won Kang; Sun Jin Kuean; Bae Jin Ha
Bibliographic Citation
BMB Reports, vol. 29, no. 5, pp. 429-435
Publication Year
1996
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.
Keyword
cyclic hexapeptideguinea pig tracheaL-659,877Neurokinin-2 (NK-2)antagonist
ISSN
1225-8687
Publisher
Korea Soc-Assoc-Inst
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.