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the form of the free amine but fluoresces when protonated. This fluorescence readout system can be applied both in parallel solution phase assays and in single-bead assays. In the later approach beads were co-functionalized with the pH sensor and the potential catalyst. The compounds were then screened for activity in acylation reactions of alcohols with acetic anhydride, a reaction that can easily be monitored, because acetic acid is released in the acyl transfer reaction and triggers the fluorescence response.

The testing of a 7.5 x 106 membered octapeptide library with fixed N-terminal rc-(CH3)-histidine (Pmh) and C-terminal alanine resulted in identification of catalysts with higher activity than DMAP for the acetylation of sec-phenylethanol [17]. The identified catalyst Boc-Pmh-L-Asn(Trt)-D-Val-L-His(Trt)-D-Phe-D-Val-D-Val-L-Ala-resin 10 then served as a parent compound for a second-generation library. This screening yielded catalysts with yet greater activity and specificity. Interestingly, all

non-fluorescent

Fig. 5.4.6. pH-Sensitive fluorescence indicators.

fluorescent non-fluorescent

Fig. 5.4.6. pH-Sensitive fluorescence indicators.

fluorescent catalysts were even more active and selective when tested in homogeneous solution. The catalysts with the highest activity also had the highest selectivity for one enantiomer of phenylethanol over the other. Thus although the assay was designed to screen for catalytic activity only it also identified, at the same time, catalysts with high selectivity.

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