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0Hsch3

Linezolid

Figure 6.12. Structures of several other antibiotics whose 3D structures have been solved in corn-' plex with either 30s or 50s, and the novel synthetic antibiotic linezolid.

0Hsch3

Clindamycin

Linezolid

Figure 6.12. Structures of several other antibiotics whose 3D structures have been solved in corn-' plex with either 30s or 50s, and the novel synthetic antibiotic linezolid.

(119), which also inhibits ribosome function (120-123), and the log of their estimated n-octanol/water partition coefficients (LogP). Estimated LogP values range from -7.2 for paromomycin to 2.8 for erythromycin for fully protonated drugs. The values for the same compounds in their neutral forms range from -4.1 to 4.6. It is interesting and not surprising to note that the two most hydrophobic compounds, erythromycin and clindamycin, seem from their crystal structures to engage in mostly hydrophobic interactions with the ribosome, whereas the most hydrophiliccompounds, paromomycin, gentamicin,hygromycin B, and streptomycin, all interact extensively with backbone phosphates through amino groups. The structure of linezolid in complex with 50S has not been solved, but if this trend holds true, then linezolid should interact with the ribosome pri marily through hydrophobic interactions. As a group these LogP values tend to be lower (more negative) than the LogP values for most drugs, which may reflect the type of interactions that are observed between antibiotics and RNA, but may also reflect the more hydrophilic nature of the surrounding RNA. RNA, even in tightly packed structures, is extensively hydrated, whereas the core of proteins is not. In a more environment the magnitude of some non-bonded interactions, such as Coulom-bic forces, will be dampened, but others, such as the hydrophobic effect, will be enhanced, hinting that the relative values that contribute to ligand/receptor associations may be different for RNA and protein targets. Numerous high-resolution protein/RNA complexes exist in the crys-tallographic database. Comparison between forces that mediate protein/protein association

Table 6.1 "Rule of 5" Values for Selected UNA Binding Antibiotics

Compound

LogPa

NH + OHb

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