Topological diversity of artificial beta-barrels in water.
Rigid-rod beta-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 beta-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 beta-barrels of different length was determined by denaturation with guanidinium chloride. Free energies of delta GH2O = -5.2 kcalmol-1, delta GH2O = -2.9 kcalmol-1, and delta GH2O < -0.3 kcalmol-1 found for homologous p-octiphenyl, p-sexiphenyl, and p-quarterphenyl beta-barrels demonstrated strong dependence of beta-barrel stability on beta-barrel length. These results revealed a very qualitative minimal (approximately 23 A) and an "ideal" beta-barrel length (approximately 34 A), synergistic formation (alpha = 1.4) and remarkable stability for "ideal" p-octiphenyl beta-barrels exceeding that of several proteins and most synthetic models. Rigid-rod beta-barrels with p-oligophenyl "staves" longer than approximately 34 A will be very difficult to make and study because of rapidly decreasing rod solubilities. However, a strategy to bypass this apparent upper limitation of beta-barrel length is introduced: supramolecular matching of mismatched rods yielded elongated beta-barrels (61 A) of acceptable stability (delta GH2O = 2.2 - 3.1 kcalmol-1).
Das
G
G
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
Matile
S
S
D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011506:Proteins / Q000138:chemical synthesis / Q000737:chemistry / Q000648:ultrastructure*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry*
D011506:Proteins; D014867:Water