NEW PHOTOAFFINITY-LABELED AGONISTS OF BRADYKININ

Citation
T. Steinmetzer et al., NEW PHOTOAFFINITY-LABELED AGONISTS OF BRADYKININ, Biological chemistry Hoppe-Seyler, 376(1), 1995, pp. 25-32
Citations number
46
Categorie Soggetti
Biology
ISSN journal
01773593
Volume
376
Issue
1
Year of publication
1995
Pages
25 - 32
Database
ISI
SICI code
0177-3593(1995)376:1<25:NPAOB>2.0.ZU;2-N
Abstract
Several photoaffinity labelled agonists of the peptide hormone bradyki nin (BK) were synthesized by solid phase methods, Their biological act ivities and binding affinities were determined in both the isolated ra t uterus (RUT) and guinea pig ileum (GPI), As photoreactive groups p-b enzoyl-phenylalanine (Bpa) and the arylazides azidobenzoic acid (ABA) and azidosalicylic acid (ASA) were attached to the N-terminus of the B K agonists. In addition, Spa was incorporated at different positions o f the BK sequence. Three different types of BK agonists were used, Fir stly, the photolabels ASA and ABA were attached to BK or to Lys-BK (ka llidin). Secondly, tyrosine containing BK analogues, suitable for radi oiodination, were labelled, This series is derived from the naturally occurring analogue phyllokinin [BK-Ile-Tyr(SO3H)] and from BK analogue s with tyrosine at position 0 and 3, The third series includes several analogues with D-N-methyl-phenylalanine (D-NMe-Phe) at position 7,whi ch selectively discriminate between the RUT and GPI bradykinin Bp rece ptors, Among the photoaffinity labelled BK agonists, the iodinatable L ys(ASA)-BK (50.8% on RUT, 73.0% on GPI), ASA-BK (26.3% on RUT), Bpa-BK -Ile-Tyr (13.6% on RUT, 14.0% on GPI) and the iodinated [D-Bpa(-1), 3- I-Tyr(0)]-BK (15.5% on RUT, 19.0% on GPI) retained a relatively high b iological activity compared with BK (100%), Thus, although BK agonists are known to allow only very restricted modifications without a stron g reduction in biological activity, these compounds should be useful c andidates for receptor labelling,