Ribosome structure and protein synthesis inhibitors

A protein synthesis inhibitor comprising:

• a first binding domain having a surface that mimics or duplicates a surface of a known first molecule that binds with a first contact site in a large ribosomal subunit;
• and
• a second binding domain having a surface that mimics or duplicates a surface of a known second molecule that binds with a second contact site in the ribosomal subunit,
• wherein the first domain is attached to the second domain so as to permit both the first domain and the second domain to bind with its respective contact site thereby to disrupt protein synthesis in a ribosomal subunit, and wherein the protein synthesis inhibitor has a molecular weight of less than about 1,500 and an IC50 lower than about 50 μM.

A protein synthesis inhibitor comprising:

• a molecule capable of contacting at least three residues but less than thirteen residues in Table 11A that together define an anisomycin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than twenty residues in Table 12A that together define a blasticidin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than sixteen residues in Table 13A that together define a carbomycin A binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than twenty residues in Table 14A that together define a tylosin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than nine residues in Table 15A that together define a sparsomycin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than thirteen residues in Table 16A that together define a virginiamycin M binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than fifteen residues in Table 17A that together define a spiramycin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than thirteen residues in Table 18A that together define an erythromycin binding pocket of a large ribosomal subunit;
• a molecule capable of contacting at least three residues but less than eleven residues in Table 19A that together define an azithromycin binding pocket of a large ribosomal subunit;
• or
• a molecule capable of contacting at least three residues but less than fifteen residues in Table 20A that together define a linezolid binding pocket of a large ribosomal subunit.