Templated parallel beta-sheets in hybrid-peptide polyamides.

摘要

Current synthetic macromolecules do not possess the high functionality and architectural control inherent in natural biopolymers such as proteins. Novel hybrid-peptide polyamides consisting of defined crystalline segments and amorphous segments are proposed. The crystalline segments are composed of peptide strands linked to rigid phenoxathiin units, which are designed to enforce the folding of the peptide strands into parallel {dollar}beta{dollar}-sheets. Flexible linkers are incorporated as the amorphous segments in the hybrid-polymers.; Amino acid and peptidic derivatives of 2,8-dimethylphenoxathiin-4,6-dicarboxylic acid were synthesized to test the effectiveness of the phenoxathiin moiety as a template for parallel {dollar}beta{dollar}-sheets. Dilute solution FTIR and {dollar}sp1{dollar}H NMR studies showed that nucleation and propagation of hydrogen bonding is greatly facilitated by the template. Detailed ROESY experiments revealed that non-degenerate peptide derivatives of 2,8-dimethylphenoxathiin-4,6-dicarboxylic acid form an unusual yet stable parallel sheet conformation in organic solvents, in which the carbonyl dipoles are all parallel.; Novel hybrid polymers were synthesized via interfacial and solution polymerization techniques. Inherent viscosity measurements and gel-permeation chromatography indicated the formation of relatively high molecular weight materials. Solid state FTIR spectra showed that the predominant secondary structural elements found in the building blocks are retained in the polymers. Amide I peaks due to the presence of parallel and antiparallel {dollar}beta{dollar}-sheets dominate the IR spectra in this region. FTIR studies on the monomers showed that the rigid phenoxathiin diacid template is required for parallel {dollar}beta{dollar}-sheet formation. The hybrid materials have higher thermal stabilities compared to natural silk fibroin with {dollar}Tsb{lcub}rm d{rcub}{dollar}, {dollar}sb{lcub}rm onset{rcub}{dollar}'s ranging from 278-313{dollar}spcirc{dollar}C. DSC studies showed that the {dollar}Tsb{lcub}rm g{rcub}{dollar}'s of the polymers were greatly influenced by the linkers incorporated into the polymer chains: {dollar}Tsb{lcub}rm g{rcub}{dollar}'s decreased with increasing flexibility of the linkers. Powder X-ray diffraction patterns of the unoriented polymers were found to be similar to other silk-like polymers.; Rigid phenoxathiin templates were also used to preorganize metal-ion binding sites in hybrid-peptides containing the LeuGlnPro sequence. Binding studies in acetonitrile showed that these hybrid-peptides bind calcium ions with association constants between 6.6 {dollar}times{dollar} 10{dollar}sp4{dollar} and 1.0 {dollar}times{dollar} 10{dollar}sp5{dollar} M{dollar}sp{lcub}-1{rcub}{dollar}.