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Biocompatibility, low toxicity and high selectivity towards bacterial cells has been the hallmark of peptide-based antibiotics. The innate immune system has been employing such molecular systems against invading pathogens as a successful defense strategy. In this study, we attempt to develop topologically constrained antimicrobial peptides with syndiotactic stereochemical arrangement, by incorporating L and D amino acids successively in its amino acid sequence. Acetylated versions of the designed peptides were also examined for its influence on bactericidal potency, against Gram-positive and Gram-negative bacteria. Syndiotactic stereochemical arrangement of the polypeptide main chain mimics stereochemistry of Gramicidin, a naturally occurring antimicrobial peptides. Gramicidin is a class of penta-deca-peptides isolated from soil bacteria Bacillus brevis, but their utility as antibiotic was limited to topical use due to high levels of hemotoxicity. Activity profiles of the four de novo designed peptide variants show higher specificity towards Gram-positive bacteria than Gram-negative variants, matching earlier reports on the therapeutic potential of gramicidin as a broad spectrum antibiotic. Significantly, our hemolytic assay confirms very low (<1%) levels of toxicity for the designed peptides unlike gramicidin. Earlier reports confirm that incorporation of D amino acids effectively negates the possibility of proteolytic degradation, thus pointing to the potential utility of de novo designed peptides with diversified stereochemistry as a promising new approach in the generation of novel antibiotic peptides. [ABSTRACT FROM AUTHOR]

Linear poly(methylphenylsiloxane) (PMPS) was prepared by the living anionic ring-opening polymerization of cis-2,4,6-trimethyl-2,4,6-triphenylcyclotrisiloxane ( cis-P). The resulting linear PMPS was shown by NMR to be highly stereoregular and remarkably high in meso-meso fraction and proposed isotactic content (~80%). Tetrahydrofuran (THF) was used as the solvent and it is noted that THF also acts as a promoter for the system by increasing the reactivity of the silanolate nucleophile at the end of the propagating chain. It is proposed that this increase in the reactivity occurs preferentially in the intermolecular (propagating) reaction. The evidence for this proposed hypothesis is the exclusive production of meso-meso and meso-racemic triads in the linear PMPS as evidenced by NMR. As the reaction temperature was increased, the rate of polymerization increased and yet the tacticity of the polymer was not affected. It is therefore clear that there was no significant amount of back-biting (intramolecular) reaction for the temperatures and time intervals studied here, despite the fact that ring-chain equilibration is commonly observed in ring-opening siloxane polymerizations. Had the reversion reaction been present, then scrambling of the chain stereoregular sequences would have been observed by an equilibration mechanism. It is well established that phenyl-phenyl interactions ( π- π stacking) can stabilize certain local conformations in PMPS chains and hence we propose that these phenyl-phenyl interactions may prevent back-biting reactions for PMPS under the kinetic conditions employed here. [ABSTRACT FROM AUTHOR]