Most proteins and large polypeptides have hydrophobic regions at their surface. These hydrophobic "patches" are due to the presence of the side chains of hydrophobic or nonpolar amino acids such as phenylalanine, tryptophan, alanine, and methionine. These surface hydrophobic regions are interspersed between more hydrophilic and polar regions, and the number, size, and distribution of them are a specific characteristic of each protein. Hydrophobic interaction chromatography (HIC) is a commonly used technique that exploits these hydrophobic features of proteins as a basis for their separation even in complex biological mixtures (Queiroz et al., J Biotechnol 87:143-159, 2001; Eisenberg and McLachlan, Nature 319:199-203, 1986). In general, the conditions under which HIC is used are relatively mild and "protein friendly" resulting in good biological recoveries. Hydrophobic binding is relatively strong and is maintained even in the presence of chaotropic agents, organic solvents, and detergents. For these reasons, this technique has a widespread use for the purification of proteins and large polypeptides.