The kinetics of formation of the silicate cubic octamer, Q(3)(8), in aqueous tetramethylammonium (TMA) silicate solutions was investigated by (29)Si NMR. The rate equation for solutions at pH 13.2-13.6 is d[Q(3)(8)]/dt = k(f) [H(+)](1.6)(+/-)(0.1)[TMA(+)](0.36)(+/-)(0.08)[Si](0.8)(+/-)(0.3) where k(f) = (2.2 +/- 0.8) x 10(16) mol(-)(1.8) kg(1.8) s(-)(1) at 296 K. The findings prove unequivocally that alkylammonium cations participate directly in the formation and subsequent stabilization of cagelike polysilicate anions. This implies a radically different mechanistic role than "templating" for alkylammonium cations in the synthesis of molecular sieves.

The addition of tetraalkylammonium cations to aqueous silicate solutions enhances the abundance of symmetric, cagelike, polysilicate anions including the cubic octamer, Si(8)O(20)(8)(-). The equilibrium ratio of tetramethylammonium (TMA) cations to the octameric silicate anion is 8:1 for solutions with a concentration ratio [OH(-)]:[Si] >/= 1:1. Evidence indicates that organocations directly associate with cagelike polyanions to form a protective shell of hydrophobic hydration that impedes hydrolysis of the central anion.

Streptococcus mutans secretes and utilizes a 21-amino-acid signaling peptide pheromone to initiate quorum sensing for genetic competence, biofilm formation, stress responses, and bacteriocin production. In this study, we designed and synthesized a series of truncated peptides and peptides with amino acid substitutions to investigate their structure-activity relationships based on the three-dimensional structures of S. mutans wild-type signaling peptide UA159sp and C-terminally truncated peptide TPC3 from mutant JH1005 defective in genetic competence. By analyzing these peptides, we demonstrated that the signaling peptide of S. mutans has at least two functional domains. The C-terminal structural motif consisting of a sequence of polar hydrophobic charged residues is crucial for activation of the signal transduction pathway, while the core ␣-helical structure extending from residue 5 to the end of the peptide is required for receptor binding. Peptides in which three or more residues were deleted from the C terminus did not induce genetic competence but competitively inhibited quorum sensing activated by UA159sp. Disruption of the amphipathic ␣-helix by replacing the Phe-7, Phe-11, or Phe-15 residue with a hydrophilic residue resulted in a significant reduction in or complete loss of the activity of the peptide. In contrast to the C-terminally truncated peptides, these peptides with amino acid substitutions did not compete with UA159sp to activate quorum sensing, suggesting that disruption of the hydrophobic face of the ␣-helical structure results in a peptide that is not able to bind to the receptor. This study is the first study to recognize the importance of the signaling peptide C-terminal residues in streptococcal quorum sensing.

Soricidin is a 54-amino acid peptide found in the paralytic venom of the northern short-tailed shrew (Blarina brevicauda) and has been found to inhibit the transient receptor potential of vallinoid type 6 (TRPV6) calcium channels. We report that two shorter peptides, SOR-C13 and SOR-C27, derived from the C-terminus of soricidin, are high-affinity antagonists of human TRPV6 channels that are up-regulated in a number of cancers. Herein, we report molecular imaging methods that demonstrate the in vivo diagnostic potential of SOR-C13 and SOR-C27 to target tumor sites in mice bearing ovarian or prostate tumors. Our results suggest that these novel peptides may provide an avenue to deliver diagnostic and therapeutic reagents directly to TRPV6-rich tumors and, as such, have potential applications for a range of carcinomas including ovarian, breast, thyroid, prostate and colon, as well as certain leukemia's and lymphomas.

Pleurocidin is an antimicrobial peptide that was isolated from the mucus membranes of winter flounder (Pseudopleuronectes americanus) and contributes to the initial stages of defense against bacterial infection. From NMR structural studies with the uniformly (15)N-labeled peptide, a structure of pleurocidin was determined to be in a random coil conformation in aqueous solution whereas it assumes an alpha-helical structure in TFE and in dodecylphosphocholine (DPC) micelles. From (15)N relaxation studies, the helix is a rigid structure in the membrane-mimicking environment. Strong NOESY cross-peaks from the pleurocidin to the aliphatic chain on DPC confirm that pleurocidin is contained within the DPC micelle and not associated with the surface of the micelle. From diffusion studies it was determined that each micelle contains at least two pleurocidin molecules.

In this study, we constructed and evaluated a target-specific, salt-resistant antimicrobial peptide (AMP) that selectively targeted Streptococcus mutans, a leading cariogenic pathogen. The rationale for creating such a peptide was based on the addition of a targeting domain of S. mutans ComC signaling peptide pheromone (CSP) to a killing domain consisting of a portion of the marine-derived, broad-spectrum AMP pleurocidin to generate a target-specific AMP. Here, we report the results of our assessment of such fusion peptides against S. mutans and two closely related species. The results showed that nearly 95% of S. mutans cells lost viability following exposure to fusion peptide IMB-2 (5.65 M) for 15 min. In contrast, only 20% of S. sanguinis or S. gordonii cells were killed following the same exposure. Similar results were also observed in dual-species mixed cultures of S. mutans with S. sanguinis or S. gordonii. The peptide-guided killing was further confirmed in S. mutans biofilms and was shown to be dose dependent. An S. mutans mutant defective in the CSP receptor retained 60% survival following exposure to IMB-2, suggesting that the targeted peptide predominantly bound to the CSP receptor to mediate killing in the wild-type strain. Our work confirmed that IMB-2 retained its activity in the presence of physiological or higher salt concentrations. In particular, the fusion peptide showed a synergistic killing effect on S. mutans with a preventive dose of NaF. In addition, IMB-2 was relatively stable in the presence of saliva containing 1 mM EDTA and did not cause any hemolysis. We also found that replacement of serine-14 by histidine improved its activity at lower pH. Because of its effectiveness, salt resistance, and minimal toxicity to host cells, this novel target-specific peptide shows promise for future development as an anticaries agent.

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Members of the fusion-associated small transmembrane (FAST) protein family are a distinct class of membrane fusion proteins encoded by nonenveloped fusogenic reoviruses. The 125-residue p14 FAST protein of reptilian reovirus has an ϳ38-residue myristoylated Nterminal ectodomain containing a moderately apolar Nproximal region, termed the hydrophobic patch. Mutagenic analysis indicated sequence-specific elements in the N-proximal portion of the p14 hydrophobic patch affected cell-cell fusion activity, independent of overall effects on the relative hydrophobicity of the motif. Circular dichroism (CD) of a myristoylated peptide representing the majority of the p14 ectodomain suggested this region is mostly disordered in solution but assumes increased structure in an apolar environment. From NMR spectroscopic data and simulated annealing, the soluble nonmyristoylated p14 ectodomain peptide consists of an N-proximal extended loop flanked by two proline hinges. The remaining two-thirds of the ectodomain peptide structure is disordered, consistent with predictions based on CD spectra of the myristoylated peptide. The myristoylated p14 ectodomain peptide, but not a nonmyristoylated version of the same peptide nor a myristoylated scrambled peptide, mediated extensive lipid mixing in a liposome fusion assay. Based on the lipid mixing activity, structural plasticity, environmentally induced conformational changes, and kinked structures predicted for the p14 ectodomain and hydrophobic patch (all features associated with fusion peptides), we propose that the majority of the p14 ectodomain is composed of a fusion peptide motif, the first such motif dependent on myristoylation for membrane fusion activity.Complex, multimeric viral fusion proteins mediate the fusion of viral envelopes to target cell membranes during virus entry into cells (1). Membrane destabilization during the fusion process is dependent on a fusion peptide motif contained within these enveloped virus fusion proteins (2-4). Fusion peptides are moderately hydrophobic stretches of ϳ20 amino acids, frequently rich in glycine and alanine residues (3, 5, 6). In the case of the class I fusion proteins typified by influenza hemagglutinin (HA), 1 human immunodeficiency virus gp41, and the F proteins of paramyxoviruses, the fusion peptide motifs are located at the N terminus of the fusion polypeptide (4). Conversely, these motifs are embedded internally within the amino acid sequence of the class II fusion proteins (e.g. alphaviruses and flaviviruses) and the G protein of vesicular stomatitis virus (VSV) (7,8). Structural predictions for fusion peptides based on CD or infrared spectroscopy have yielded conflicting results (9 -12) and are influenced by the different methods used for preparation of the water-insoluble, flexible fusion peptide (13). The properties of conformational flexibility and environmentally induced structural changes may represent essential features of fusion peptides, intimately linked to their function in the fusion process (4,14,15).To deal with ...