Structure-Activity Relationship among Bridged Monobactams

9 Structure-Activity Relationship among Bridged Monobactams 

5 Structure-Based Design of Potent Beta-Lactamase Inhibitors 

Optimization of these interactions described above through modification of the acyl side chain increased the affinity over lO -fold, from a value 10 mM (when none of the interactions are satisfied) to a Km value of 120 nM (for Ro-46-7649 9). The stability of the acyl-enzyme complex also increased (Table 1), possibly because tighter binding of the inhibitor decreases the flexibility of the acyl-enzyme complex and thus the rate of occasional access of water to the ester. 

2-deoxy-2,3-didehydro-A acetyl-D-neuraininic acid 2-3-didehydro-2,4-dideoxy-4-amino-iV-acetyl-D-neuraminicacid 2-3-didehydro-2,4-dideoxy-4-guanidino-iV-acetyl-D-neuraminic acid 

Influenza viruses belong to the orthomyxoviridae family. There are three types of influenza virus, named A, B and C (from the chronological order of their characterization). A multitude of subtypes have been characterized for type A virus. These have arisen from the antigenic cross-reactivities of the surface glycoproteins (see below). No subtypes have been identified for types B and C. Influenza type C virus is significantly different to the other two and in this work only influenza viruses A and B are discussed. Influenza virus particles are spherical in shape, approximately 100 nm in diameter. A schematic diagram of the virus is shown in Fig. 1. 

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