Topological diversity of artificial β‐barrels in water

Rigid‐rod β‐barrels are composed of interdigitating, short, amphiphilic peptide strands flanked by stabilizing rigid‐rod “staves”. We here report studies on the topological diversity of these recently devised artificial β‐barrels with regard to their length. For this purpose, homologous p ‐octiphenyl, p ‐sexiphenyl, and p ‐quarterphenyl rods were equipped with complementary tripeptide strands based on the sequences Lys‐Leu‐Lys and Glu‐Leu‐Glu. The stability of rigid‐rod β‐barrels of different length was determined by denaturation with guanidinium chloride. Free energies of Δ G   H   2 O= −5.2 kcalmol −1 , Δ G   H   2 O= −2.9 kcalmol −1 , and Δ G   H   2 O< −0.3 kcalmol −1 found for homologous p ‐octiphenyl, p ‐sexiphenyl, and p ‐quarterphenyl β‐barrels demonstrated strong dependence of β‐barrel stability on β‐barrel length. These results revealed a very qualitative minimal (∼23 Å) and an “ideal” β‐barrel length (∼34 Å), synergistic formation (α = 1.4) and remarkable stability for “ideal” p ‐octiphenyl β‐barrels exceeding that of several proteins and most synthetic models. Rigid‐rod β‐barrels with p ‐oligophenyl “staves” longer than ∼34 Å will be very difficult to make and study because of rapidly decreasing rod solubilities. However, a strategy to bypass this apparent upper limitation of β‐barrel length is introduced: supramolecular matching of mismatched rods yielded elongated β‐‐barrels (61 Å) of acceptable stability (Δ G   H   2 O= 2.2 − 3.1 kcalmol −1 ). Chirality 13:170–176, 2001. © 2001 Wiley‐Liss, Inc.