Reexamining Povarov Reaction’s Scope and Limitation in the Generation of HCV-NS4A Peptidomimetics

Figure 2

Design of THN scaffold as potential NS4A peptidomimetic. (a) Binding features of the NS4A with amino acids in the NS3. Important hydrogen bonding interactions are shown in yellow lines. H-bond lengths are shown in Å length units, and they were measured between heavy atoms. (b) Alignment of the designed core THN (golden color) with the NS4A core region bound to NS3. Circles illustrate good fit of R¹ and R² with the cofactor side chains. (c) Sketch of the designing method of THN to mimic the core part of NS4A. The bold bonds highlight the planar area in the kink region of NS4A that was transformed to a bicyclic structure in the designed peptidomimetic THN scaffold. Similarly, colored heteroatoms represent equivalent replacements.

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