Cyclic peptides as molecular adapters for a pore-forming protein

Recently, cyclodextrins were shown to act as adapters for the pore-forming protein staphylococcal alpha -hemolysin (alpha HL). The bagel-shaped molecu les: bind in the lumen of the transmembrane channel formed by alpha HL and alter the properties of the pore. For example, the unitary conductance is r educed, and organic molecules can act as channel blockers by binding to the cavity within the cyclodextrin adapter, In a search for a class of adapter s more versatile than the cyclodextrins and amenable to preparation as libr aries, 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)-] (diNH(3)(+)-(FA)(4)), and cyclo(-L-Ph e-D-N-(carboxymethyl)-Ala-L-Phe-D-Ala)(2)-] (diCO(2)(-)-(FA)(4)), became lo dged within the alpha HL pore, altering the unitary conductance and ion sel ectivity. Further, the positively charged peptides, (RL)(4) and diNH(3)(+)- (FA)(4), were able to act as binding' sites for various small polyanions. F or example, the second messenger IP3 bound to (RL)(4) within the aHL pore. Therefore, the modulation of single-channel currents through pores containi ng cyclic peptide adapters may prove useful for. sensing a variety of molec ules.