Synthesis and microbiological activities of some monohalogenated analogs of tyrosine

Abstract

2-Chlorotyrosine and 2-bromotyrosine, as well as the previously reported 2-fluorotyrosine, were synthesized by hydrolysis of the condensation products from the appropriate benzyl bromide and ethyl acetamidomalonate and were compared with the corresponding 3-halotyrosines as growth inhibitors of Escherichia coli 9723, Streptococcus faecalis 8043 and Lactobacillus plantarum 8014. In contrast to the 2- and 3-fluorotyrosines which were equally effective as growth inhibitors, the 2-chloro- and 2-bromotyrosines were much more effective than the 3-chloro- and 3-bromotyrosines in inhibiting the growth of the three microorganisms. For each of the assay organisms, the growth inhibitions of all three 2-halotyrosines were reversed competitively in varying degrees by tyrosine.

Fluorinated amino acids: compatibility with native protein structures and effects on protein–protein interactions

“…It may be worth mentioning that when employing fluorinated Tyr analogues for biological applications, one has to consider that 3-FTyr and 2-FTyr were seen to antagonize tyrosine utilization competitively in several biological systems. 119,120 Furthermore, 3-FTyr is enzymatically converted in the cellular milieu to fluorinated intermediates of the tricarboxylic acid cycle (fluoroacetate and fluorocitrate) via the tyrosine pathway. 121,122 As a consequence, its administration in test animals has had lethal effects.…”

Eosinophils generate brominating oxidants in allergen-induced asthma

“…Alternatively, it is tempting to speculate that EPO-dependent bromination of tyrosine residues evolved because it may confer an activity that contributes to host defenses. Multiple distinct brominated halometabolites (including brominated tyrosine analogs) possessing antimicrobial activities have been identified in marine organisms such as algae, sponges, bryozoans, tunicates, worms, and molluscs (48)(49)(50)(51)(52)(53)(54)67). Synthesis of these halometabolites is thought to be catalyzed by distinct bromoperoxidases that, unlike the hemoprotein EPO, utilize vanadium at their catalytic centers.…”

Precursor-directed biosynthesis of fluorinated iturin A in Bacillus spp.

“…The inhibition of microbial growth by 2-and 3fluorotyrosine has been observed. 11 Analysis of the CS93 supernatant by 19 F nuclear magnetic resonance spectroscopy revealed that no degradation of the fluorotyrosine occurred (not shown), thus the extended lag period was most likely due to the growth of a small number of fluorotyrosine-resistant bacteria in the inoculum. This suggestion is supported by the observation that when fresh medium containing fluorotyrosine was inoculated from a culture previously exposed to the compound, no inhibition of growth was observed (Fig.…”