The Development of Novel Antibiotics Using ... - Jacobs University

Introduction
Addition of Schistosoma japonicum glutathione-S-transferase (SjGST) amplifies library member
54. This approach is a good example for enzyme-directed amplification in a DCL. At low pH the
reaction becomes slow and irreversible allowing switching off the DCL.
Figure 1.12 A DCL generated from GSH analogues 49-52 and EA.
1.3.8 Alkene metathesis
Carbonic anhydrase II (CA) are family of Zn-containing enzymes, which catalyze the interconversions
of bicarbonate ions (HCO – 3 ) and carbon dioxide, which forms in high levels in almost
all metabolic processes. Some antitumor drugs function by inhibiting Zn-containing enzymes.
The mechanism of inhibition for CA proceeds through recognition of the sulfonamide moiety in
the structure core of the inhibitor. Poulson and Bornaghi reported on generation of a DCL via
cross metathesis olefin approach using an immobilized Grubbs first generation catalyst. 52 The
authors demonstrated the recognition affinity of 58 to CA enzyme from the screened library
members (Figure 1.13).
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