18 Pages

Positional Scanning Deconvolution


A. Peptidomimetic combinatorial libraries An example of the concept of chemical transformation has been carried out through the exhaustive alkylation of existing peptide libraries to prepare N-alkyl peptidomimetic libraries (26) (Figure 4). Examples are shown in Figure 4. The library format, the type of chemical transformation and the molecular diversity are outlined in Table 1. Initially, a peptidomimetic library (row 1 in Table 1) resulting from the permethylation of a positional scanning hexapeptide library and containing L-amino acids as building blocks was prepared. From this library, compounds were found having potent antimicrobial activity against Staphylococcus aureus (permethylated FFIFFF-NH2, IC50 = 6 mg/mL), while the parent library of peptides showed little activity.