Recently, cyclodextrins were shown to act as adapters for the pore-forming protein staphylococcal α-hemolysin (αHL). The bagel-shaped molecules bind in the lumen of the transmembrane channel formed by αHL and alter the properties of the pore. For example, the unitary conductance is reduced, and organic molecules can act as channel blockers by binding to the cavity within the cyclodextrin adapter. In a search for a class of adapters more versatile than the cyclodextrins and amenable to preparation as libraries, cyclic peptides have now been examined. Four peptides, cyclo[(l-Arg-d-Leu)4-] ((RL)4), cyclo[(l-Glu-d-Leu)4-] ((EL)4), cyclo[(-l-Phe-d-N-(aminoethyl)-Ala-l-Phe-d-Ala)2-] (diNH3+-(FA)4), and cyclo[(-l-Phe-d-N-(carboxymethyl)-Ala-l-Phe-d-Ala)2-] (diCO2--(FA)4), became lodged within the αHL pore, altering the unitary conductance and ion selectivity. Further, the positively charged peptides, (RL)4 and diNH3+-(FA)4, were able to act as binding sites for various small polyanions. For example, the second m...