Total Liquid-phase Sythesis, Head-to-tail Cyclization and Synergistic Self-cleavage of Peptide on Small-molecular Supports

To achieve the synthesis of head-to-tail cyclic peptides via the liquid-phase on-support cyclization and synergistic self-cleavage strategy, 4,4’-bis(diphenylphosphinyloxyl) diphenyl ketoxime (BDKO) and 4-diphenyl phospholoxy benzyl alcohol (DPBA) were designed and prepared as small-molecular supports for greener peptide synthesis. During liquid-phase peptide synthesis on BDKO (or DPBA) support for peptide chain extension by Boc protocol, the last amino acid at the N-terminus of the peptide chain ends with a Fmoc protected amino acid. With the removal of the Fmoc group, head-to-tail cyclization and self-cleavage of the peptide chain synchronously occurred on BDKO (or DPBA) support to release the target cyclic peptide and the original support itself. They can be easily separated and purified, and the support can be recycled for reusing directly. The total synthesis of naturally occurring cyclic peptides such as Mortiamide A-E, Gramicidin S and cyclo(Phe-Pro) on BDKO (or DPBA) support in a resin-free manner was successfully demonstrated

Optimization of antibacterial cyclic decapeptides

A previously developed method for cyclic peptide synthesis was demonstrated to be able to provide convenient access to large combinatorial libraries of analogues, and this methodology was applied to the optimization of natural product cyclic decapeptides. Using this method, a 192-member library was designed and successfully constructed on the basis of the natural products tyrocidines, streptocidins, and loloatins to increase the therapeutic indices of these antibiotics. Library screening identified nine analogues whose therapeutic indices were increased by up to 90-fold in comparison to the natural products. Three of these analogues showed significant increase in antibacterial potency and concurrent drastic decrease in hemolytic activity. Since the natural products target the bacterial cell wall, the newly discovered analogues are promising leads for drug development against drug-resistant bacteria

Dissociation of antibacterial and hemolytic activities of an amphipathic peptide antibiotic

Using an alanine-scanning method, we have found that the antibacterial and hemolytic activities of the amphipathic cyclic decapeptide antibiotic tyrocidine A depend on different structural components. Single substitution of glutamine-6 of the natural product with a cationic amino acid results in a therapeutic index enhancement of up to 140-fold. Successful dissociation of the two intimately associated properties should enable discovery of novel analogues with both high bacterial selectivity and antibacterial potency to counter microbial resistance

Electro-catalysis of carbon black or titanium sub-oxide supported Pd-Gd towards formic acid electro-oxidation

Carbon black supported Pd-Gd catalysts (Pd-xGd/C, x is weight percent in catalyst) with different amounts of Gd were prepared by a simultaneous reduction reaction with sodium borohydride in aqueous solution. The structure, morphology and element valence state of these catalysts were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS), respectively. The electro-catalytic performance of these catalysts for formic acid oxidation was investigated using cyclic voltammetry (CV), chronoamperometry (CA) and CO stripping experiments. It is found that the Pd-2.5Gd/C catalyst has a better electro-catalytic activity than the Pd/C catalyst, which can be explained by a bi-functional mechanism. In addition, the higher content of metallic Pd caused by the addition of Gd also contributes to the better catalytic activity of Pd-2.5Gd/C. Based on the good electro-catalytic performance of the Pd-2.5Gd/C, Pd-xGd/Ti4O7 (x stands for weight percentage in whole catalyst) catalysts were also prepared and characterized in the same way. The Pd-2.5Gd/Ti4O7 and Pd-4Gd/Ti4O7 catalysts exhibited better catalytic activities than the Pd-2.5Gd/C catalyst, which mainly results from the further increase of metallic Pd caused by Ti4O7.</p