The interaction of cyclodextrins (CDs) with poly(N-methacryloyltryptophan) (pMTrp) and with poly (N-methacryloylphenylalanine) (pMPhe) was investigated as a simple model system of macromolecular recognition of proteins. The association constants (K) for the model compounds, sodium salts of tryptophan and phenylalanine, are not so different (i.e. 43 and 16 M-1 for alpha-CD, 59 and 69 M-1 for P-CD, and 12 and 3 M-1 for gamma-CD, respectively). On the other hand, there is a significant difference in the apparent K values for pMTrp and pMPhe (i.e. the K values for pMPhe are considerably smaller than ca. 10 M-1, whereas those for pMTrp are 30, 83, and 11 M-1 for alpha-, beta-, and gamma-CDs, respectively). These observations indicate that a subtle difference in polymer side chains can be critical in macromolecular recognition. (c) 2006 Elsevier Ltd. All rights reserved.