Stereoelectronic tuning of the structure and stability of the trp cage miniprotein

Proline residues are critical structural elements in proteins, defining turns, loops, secondary structure boundaries, and polyproline helices. Control of proline conformation therefore may be used to define protein structure and stability. 4-Substituted proline derivatives may be used to control proline ring pucker, which correlates with protein main chain conformation. To examine the use of proline conformational restriction to tune globular protein stability, a series of peptides derived from the trp cage miniprotein was synthesized. Proline at residue 12 of the trp cage miniprotein, which adopts a Cgamma-exo ring pucker in the NMR structure, was replaced with 4-substituted proline derivatives, including 4R derivatives favoring a Cgamma-exo ring pucker and 4S derivatives favoring a Cgamma-endo ring pucker. Eight trp cage peptides were synthesized, five of which included residues that are not commercially available, without requiring any solution phase chemistry. Analysis of the trp cage peptides by circular dichroism and NMR indicated that the structure and stability of the trp cage miniprotein was controllable based on the conformational bias of the proline derivative. Replacement of Pro12 with 4S-substituted proline derivatives that favor the Cgamma-endo ring pucker destabilized the trp cage, while replacement of Pro12 with 4R-substituted proline derivatives that favor a Cgamma-exo ring pucker resulted in increased alpha-helicity and thermal stability of the trp cage. The most stable trp cage derivatives contained benzoates of 4R-hydroxyproline, which also exhibited the most pronounced stereoelectronic effects in TYProxN model peptides. Overall, the stability of the trp cage was tunable by over 50 degrees C depending on the identity of the proline side chain at residue 12.     

Classification of contractively complemented Hilbertian operator spaces

We construct some separable infinite-dimensional homogeneous Hilbertian operator spaces and , which generalize the row and column spaces R and C (the case m=0). We show that a separable infinite-dimensional Hilbertian JC^∗-triple is completely isometric to one of , , , or the space Φ spanned by creation operators on the full anti-symmetric Fock space. In fact, we show that (respectively ) is completely isometric to the space of creation (respectively annihilation) operators on the m (respectively m+1) anti-symmetric tensors of the Hilbert space. Together with the finite-dimensional case studied in [M. Neal, B. Russo, Representation of contractively complemented Hilbertian operator spaces on the Fock space, Proc. Amer. Math. Soc. 134 (2006) 475-485], this gives a full operator space classification of all rank-one JC^∗-triples in terms of creation and annihilation operator spaces.We use the above structural result for Hilbertian JC^∗-triples to show that all contractive projections on a C^∗-algebra A with infinite-dimensional Hilbertian range are “expansions” (which we define precisely) of normal contractive projections from A** onto a Hilbertian space which is completely isometric to R, C, R∩C, or Φ. This generalizes the well-known result, first proved for B(H) by Robertson in [A.G. Robertson, Injective matricial Hilbert spaces, Math. Proc. Cambridge Philos. Soc. 110 (1991) 183-190], that all Hilbertian operator spaces that are completely contractively complemented in a C^∗-algebra are completely isometric to R or C. We use the above representation on the Fock space to compute various completely bounded Banach-Mazur distances between these spaces, or Φ.     

Passive standoff detection of RDX residues on metal surfaces via infrared hyperspectral imaging

Hyperspectral images of galvanized steel plates, each containing a stain of cyclotrimethylenetrinitramine (RDX), were recorded using a commercial long-wave infrared imaging spectrometer. Demonstrations of passive RDX chemical detection at areal dosages between 16 and 90 μg/cm² were carried out over practical standoff ranges between 14 and 50 m. Anomaly and target detection algorithms were applied to the images to determine the effect of areal dosage and sensing distance on detection performance for target RDX. The anomaly detection algorithms included principal component analysis, maximum autocorrelation factors, and principal autocorrelation factors. Maximum difference factors and principal difference factors are novel multivariate edge detection techniques that were examined for their utility in detection of the RDX stains in the images. A target detection algorithm based on generalized least squares was applied to the images, as well, to see if the algorithm can identify the compound in the stains on the plates using laboratory reflection spectra of RDX, cyclotetramethylenetetranitramine (HMX), and 2,4,6-trinitrotoluene (TNT) as the target spectra. The algorithm could easily distinguish between the nitroaromatic (TNT) compound and the nitramine (RDX, HMX) compounds, and, though the distinction between RDX and HMX was less clear, the mean weighted residuals identified RDX as the stain on the plate. Improvements that can be made in this detection technique are discussed in detail. As expected, it was found that detection was best for short distances and higher areal dosages. However, the target was easily detected at all distances and areal dosages used in this study. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The State of Elliptic Curve Cryptography

Since the introduction of public-key cryptography by Diffie and Hellman in 1976, the potential for the use of the discrete logarithm problem in public-key cryptosystems has been recognized. Although the discrete logarithm problem as first employed by Diffie and Hellman was defined explicitly as the problem of finding logarithms with respect to a generator in the multiplicative group of the integers modulo a prime, this idea can be extended to arbitrary groups and, in particular, to elliptic curve groups. The resulting public-key systems provide relatively small block size, high speed, and high security. This paper surveys the development of elliptic curve cryptosystems from their inception in 1985 by Koblitz and Miller to present day implementations.     

Polymerization-induced self-assembly and disassembly during the synthesis of thermoresponsive ABC triblock copolymer nano-objects in aqueous solution

Polymerization-induced self-assembly (PISA) has been widely utilized as a powerful methodology for the preparation of various self-assembled AB diblock copolymer nano-objects in aqueous media. Moreover, it is well-documented that chain extension of AB diblock copolymer vesicles using a range of hydrophobic monomers via seeded RAFT aqueous emulsion polymerization produces framboidal ABC triblock copolymer vesicles with adjustable surface roughness owing to microphase separation between the two enthalpically incompatible hydrophobic blocks located within their membranes. However, the utilization of hydrophilic monomers for the chain extension of linear diblock copolymer vesicles has yet to be thoroughly explored; this omission is addressed for aqueous PISA formulations in the present study. Herein poly(glycerol monomethacrylate)-poly(2-hydroxypropyl methacrylate) (G-H) vesicles were used as seeds for the RAFT aqueous dispersion polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA). Interestingly, this led to polymerization-induced disassembly (PIDA), with the initial precursor vesicles being converted into lower-order worms or spheres depending on the target mean degree of polymerization (DP) for the corona-forming POEGMA block. Moreover, construction of a pseudo-phase diagram revealed an unexpected copolymer concentration dependence for this PIDA formulation. Previously, we reported that PHPMA-based diblock copolymer nano-objects only exhibit thermoresponsive behavior over a relatively narrow range of compositions and DPs (see Warren et al., Macromolecules, 2018, 51, 8357–8371). However, introduction of the POEGMA coronal block produced thermoresponsive ABC triblock nano-objects even when the precursor G-H diblock copolymer vesicles proved to be thermally unresponsive. Thus, this new approach is expected to enable the rational design of new nano-objects with tunable composition, copolymer architectures and stimulus-responsive behavior.

Chain extension of linear AB diblock copolymer vesicles by seeded RAFT aqueous dispersion polymerization using a hydrophilic monomer C leads to polymerization-induced disassembly to form lower-order thermoresponsive ABC triblock copolymer nano-objects.     

Uncovering a CF3 Effect on X-ray Absorption Energies of [Cu(CF3)4]− and Related Copper Compounds by Using Resonant Diffraction Anomalous Fine Structure (DAFS) Measurements**

Understanding the electronic structures of high-valent metal complexes aids the advancement of metal-catalyzed cross coupling methodologies. A prototypical complex with formally high valency is [Cu(CF₃)₄]⁻ ( 1 ), which has a formal Cu(III) oxidation state but whose physical analysis has led some to a Cu(I) assignment in an inverted ligand field model. Recent examinations of 1 by X-ray spectroscopies have led previous authors to contradictory conclusions, motivating the re-examination of its X-ray absorption profile here by a complementary method, resonant diffraction anomalous fine structure (DAFS). From analysis of DAFS measurements for a series of seven mononuclear Cu complexes including 1 , here it is shown that there is a systematic trifluoromethyl effect on X-ray absorption that blue shifts the resonant Cu K-edge energy by 2–3 eV per CF₃, completely accounting for observed changes in DAFS profiles between formally Cu(III) complexes like 1 and formally Cu(I) complexes like (Ph₃P)₃CuCF₃ ( 3 ). Thus, in agreement with the inverted ligand field model, the data presented herein imply that 1 is best described as containing a Cu(I) ion with dⁿ count approaching 10.