Cyclic peptides as molecular adapters for a pore-forming protein

被引:125
作者
Sanchez-Quesada, J
Ghadiri, MR
Bayley, H
Braha, O [1 ]
机构
[1] Texas A&M Univ, Hlth Sci Ctr, Dept Med Biochem & Genet, College Stn, TX 77843 USA
[2] Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA
[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[4] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA
[5] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
关键词
D O I
10.1021/ja002436k
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Recently, cyclodextrins were shown to act as adapters for the pore-forming protein staphylococcal alpha -hemolysin (alpha HL). The bagel-shaped molecules: 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 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)-] (diNH(3)(+)-(FA)(4)), and cyclo(-L-Phe-D-N-(carboxymethyl)-Ala-L-Phe-D-Ala)(2)-] (diCO(2)(-)-(FA)(4)), became lodged within the alpha HL pore, altering the unitary conductance and ion selectivity. Further, the positively charged peptides, (RL)(4) and diNH(3)(+)-(FA)(4), were able to act as binding' sites for various small polyanions. For example, the second messenger IP3 bound to (RL)(4) within the aHL pore. Therefore, the modulation of single-channel currents through pores containing cyclic peptide adapters may prove useful for. sensing a variety of molecules.
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页码:11757 / 11766
页数:10
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