Toward catalytic rigid-rod ?-barrels: A hexamer with multiple histidines

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Abstract
Rigid‐rod β‐barrels are composed of interdigitating, short, amphiphilic peptide strands that are flanked by stabilizing rigid‐rod “staves.” As a first step toward the construction of catalytic rigid‐rod β‐barrels, we here report synthesis and study of a new barrel designed to comprise alternating leucine and histidine residues at the inner and lysine and glutamate residues at the outer barrel surface. Synthesis of p‐octiphenyls with lateral tripeptide strands followed procedures described previously. Barrel formation by programmed assembly of complementary tripeptide‐p‐octiphenyl rods was monitored by circular dichroism (CD). CD‐mixing curves (Job‐plots) were consistent with 1:1‐stoichiometry. Guanidinium chloride denaturation experiments gave a ΔGH20 = −1.8 kcal mol−1 with a C50 = 1.9 M. Size exclusion chromatography suggested quantitative formation of a hexamer. Facile barrel deconstruction by acid and divalent cations demonstrated the presence of internal, nonproximal histidines. Inclusion complex formation with fluorescent guests corroborated internal hydrophobicity of β‐barrel hosts and potential for intratoroidal catalysis. Chirality 14:18–24, 2002.