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Pathogenic infections represent a persistent threat to human health. The rapid development of resistance to drug therapies creates a continuing need for developing new anti-infective agents. Host-Defense Peptides (HDPs) represent a potential source of inspiration for development of new antibacterial agents. These peptides are produced by eukaryotes as part of the innate immune response to bacterial infection. Elucidation of high-resolution structure has been challenging for the large group of HDPs that form helices on or within membranes but do not manifest a strong folding propensity in aqueous solution. We used racemic crystallization to obtain the crystal structure of an analogue of the widely-studied HDP, magainin 2. Ala8,13,18-magainin 2 is a designed variant that displays enhanced antibacterial activity relative to the natural peptide. The crystal structure of Ala8,13,18-magainin 2, features a dimerization mode that has previously been proposed to play a role in the antibacterial activity of magainin 2 and related peptides (1).
The broad molecular diversity among HDPs suggests that their prokaryotic-selective activity is not tightly coupled to specific features of amino acid sequence or peptide conformation. This situation has inspired the development of several families of sequence-random hydrophobic-cationic co-polymers that display antibacterial behavior with varying levels of hemolytic activity. We developed a new experimental approach for exploring the impact of sample diversity on the biological activity profiles of mixtures (2). Specifically, we employed solid-phase synthesis in an unconventional way to generate peptide mixtures that contain one type of hydrophobic residue and one type of cationic residue. Each mixture was random in terms of sequence, but highly controlled in terms of chain length and stereochemistry. Analysis of the antibacterial and hemolytic properties of these mixtures revealed that selective antibacterial activity can be achieved with heterochiral binary mixtures but not homochiral binary mixtures.
We have explored nylon-3 materials (poly--peptides) as functional mimics of HDPs (4, 5). Nylon-3 polymers are readily synthesized via ring-opening polymerization of -lactams; some hydrophobic-cationic copolymers display broad antimicrobial activity. It is challenging to perform structure-activity relationships studies for nylon-3 copolymers (or other copolymers) because each sample contains many different kinds of molecules (different lengths, different subunit compositions, different subunit sequences, different subunits stereochemistries). Using our unconventional solid-phase approach we were able to prepare nylon-3 copolymer mixtures that are better defined than are the mixtures generated via ring-opening polymerization of -lactams. This synthetic strategy is not available for any other types of polymers that have been reported to function as selective antibacterial agents. Our findings show that chain length and stereochemistry are important parameters in terms of determining the activity of polymers of this type.
1. Hayouka, Z. Chakraborty, S. Liu, R. Gellman, H.S. (2013). Interplay Among Subunit Identity, Composition, Chain Length and Stereochemistry in the Activity Profile of Sequence-Random Oligomer Mixtures. J. Am. Chem. Soc. 135(32):11748-5.
2. Hayouka, Z. Mortenson, D.E. Kreitler, D.F. Weisblum, B. Forest, K.T. Gellman, H.S. (2013). Evidence for Phenylalanine Zipper-Mediated Dimerization in the X-Ray Crystal Structure of a Magainin 2 Derivative. J. Am. Chem. Soc. In press.
3. Liu, R. Chakraborty, S. Hayouka, Z. Gellman, H.S. (2013). Nylon-3 polymer as antifungal agent. J. Am. Chem. Soc. 135, 5270-3.
4. Chakraborty, S. Liu, R. Hayouka, Z. Gellman. H.S. (2013). Studying the effect of cyclic versus acyclic nylon-3 polymers. ACS macro letter.

Conventional wisdom has always held that transition states are impossible to observe and characterize experimentally. With the exceptions of ultrafast spectroscopy and ab initio electronic
structure calculations, direct information about these critical points on potential energy surfaces has therefore been very limited. We have recently demonstrated for the first time that it is possible to
characterize a transition state by high resolution spectroscopic methods, using the cis-trans isomerization in the well-known A state of acetylene as a prototypical system. New spectroscopic patterns related to the properties of transition states will be discussed, in addition to the experimental and theoretical techniques employed to decipher the complex spectra and dynamics of isomerizing molecules.

From raw data to gene or protein expression profiles, from cell populations to complex cultures, currently gene or protein expression analysis works with a variety of differently structured data. Although data visualization is closely connected with data analysis approaches; in our presentation we will specifically focus on integrated data visualization. By complementing the traditional tools such as bar charts or line graphs a tool kit of new sophisticated visualization techniques became available during the last decade. Many concerns regarded to the display of single but also complex data, exactly known but also uncertain data will be discussed. How to apply new visual approaches and applications such as proportional Euler charts, streamgraphs and Voronoi treemaps we will present and explain for a variety of examples from modern OMICs centric biology.

Studies of structure and dynamics of molecules and nanoparticles by spectroscopic methods rely on the high sensitivity of these methods to the symmetry of the investigated system. Detailed understanding of the effects of symmetry breaking in these systems is, therefore, an important task. Several scenarios where the D3h symmetry is broken to become C2v will be discussed with examples from two different (although related by the common phenomena of symmetry breaking) spectroscopic fields: (a) Nanoplasmonics and single-molecule surface-enhanced Raman spectroscopy (smSERS), and (b) Two-dimensional femtosecond vibrational spectroscopy (2D-IR). As follows from the group theory, the systems that belong to the D3h point group involve doubly degenerated spectroscopic transitions, while this degeneracy is lifted in the case of C2v. In the first part of the talk I will describe how the localized plasmon normal modes in clusters of three metallic nanoparticles depend on the cluster’s geometry and how their plasmon mode structure affects the signals measured in the smSERS experiments. These are examples of permanent breaking of symmetry in the immobilized clusters of plasmonic nanoparticles. In the second part of the talk, I will show that solvation of the molecular ion potassium tricyanomethanide, which has D3h symmetry in the gas phase, breaks this symmetry and induces ultrafast dynamical processes studied by 2D-IR spectroscopy. Splitting of the degenerate vibrational modes’ transition frequencies and the ultrafast relaxation dynamics of the new modes strongly depend on the nature of the solute-solvent interactions, as illustrated by comparison of the experimental data for the protic (water) and aprotic (dimethyl sulfoxide) solvents.