STRUCTURE-LIPOPHILICITY AND STRUCTURE-POLARITY RELATIONSHIPS OF AMINO-ACIDS AND PEPTIDES

The objectives of this study were to gain insights into the structure- lipophilicity relationships of peptides and to propose an improved mod el for estimating their lipophilicity. First, existing databases were extended to obtain the distribution coefficients of a total of 208 fre e or protected peptides (di- to pentapeptides). The polarity parameter s (Lambda) of 23 free amino acids and 19 protected amino acids (AcNH-C HR-CONH2) and of their side chains were calculated from experimental d istribution coefficients and computed molecular volumes. An analysis o f the polarity parameters revealed that the hydrophobicity of the amin o-acid side chains is largely reduced due to the polar field of the ba ckbone. The polarity parameters of the peptides were then obtained in a similar manner and shown to be highly correlated with the sum of the polarity parameters of their side chains, i.e., the lipophilicity of peptides can be calculated from their molecular volume and the sum of their side-chain polarities using the regression established for each individual series of peptides (Fig. 1). This last restriction is essen tial since the polarity and lipophilic increment of a NH-CH-CO unit w ere shown to decrease with increasing length of backbone.