An [(azidophenyl)ureido]taxoid (TaxAPU) was synthesized in a radiolabeled form by coupling an aminotaxoid to tritiated N-methyl-N-(chloroformyl)-p-azidoaniline. TaxAPU was used to photolabel polymerized porcine brain tubulin. This newly synthesized probe possesses taxoid properties as demonstrated by its effect, in the absence of light, on the kinetics of tubulin assembly and microtubule disassembly and on the critical concentration of tubulin. TaxAPU apparently competes with Taxol for the same binding site with an equilibrium dissociation constant of 6 microM. The photoactivation of 266 nm of the radiolabeled probe in the presence of microtubules led to a covalent incorporation of radioactivity. Analysis of the radiolabeled polypeptides by electrophoresis under denaturing conditions revealed a specific incorporation of tritium in both the alpha-and beta-subunits of tubulin. A dependence on probe concentration was observed for the irreversible radioactivity incorporated into both subunits and maintained essentially a ratio of 2.5:1 between beta/alpha. Therefore, TaxAPU constitutes a true photoaffinity probe for the taxoid binding site on microtubules. Our results complement those reported by Rao et al. (1992) of photo-cross-linking experiments with unmodified Taxol.

Semi-hydrogenation by 02 gas on L i n d l a r c a t a l y s t o f an a c e t y l e n i c precursor l e d t o [ l l , 12,14,15-2H4]-LTA4 methyl e s t e r -Ia. N u c l e o p h i l i c opening o f t h e epoxide r i n g by amino t h i o a c i d s afforded a f t e r saponificat i o n t h e corresponding deuterated peptidoleukotrienes LTC4, LTD4 and LTE4. -

No abstract

No abstract

The h y n t h u h 06 (BETAXOLOL) Lab&ed w i t h m b o n 14 : I -[ 4 -( 2-cychptopyL methoxyethyL-[ 1 -1 4 C ] ) phenoxy]-3-hoptoyf &no-2pfiopawb : 13 wan achieved by a &&?.h? h t e p btgUeVICe @om [ C ] c a b o n dioxide. Cmbonation w i t h I4C02 06 t h e Ghignand heagent 1 gave 4-benzyLoxy benzoic a c i d : 2 ( 8 7 % y i e l d ) . 2 wan b~C C e A b i \ i & &&ed efi dokhtion wdh-diazomahane and U t k i w n aeUminiwn hydhide giving d e t o [ 7 -' 4 C ] 4-bcnzyLoxybenzyL d c o h o d 4 ( b 2 % y i d d ) . AdcohoL 4 WM &tamdomed i n t o xhe comenponding ckeohide 5 when expobed t o thionyLckeohide i n etheh. 5 WM condenbed w i t h NaCN i n DMF t o give t h e ni,t&Le 6 which w f i hycihoPyned i n t o t h e a c i d 7 h o d a t e d i n a 75 %