Tailored photocleavable peptides: fragmentation and neutralization pathways in high vacuum.

Photocleavable tags (PCTs) have the potential for excellent spatio-temporal control over the release of subunits of complex molecules. Here, we show that electrosprayed oligopeptides, functionalized by a tailored ortho-nitroarylether can undergo site-specific photo-activated cleavage under UV irradiation (266 nm) in high vacuum. The comparison of UV photodissociation (UVPD) and collision-induced dissociation (CID) points to the thermal nature of the cleavage mechanism, a picture corroborated by the temperature dependence of the process. Two competing photodissociation pathways can be identified. In one case a phenolate anion is separated from a neutral zwitterion. In the other case a neutral phenol derivative leaves a negatively charged peptide behind. To understand the factors favoring one channel over the other, we investigate the influence of the peptide length, the nature of the phenolic group and the position of the nitro-group (ortho vs. para). The observed gas phase cleavage of a para-nitro benzylic ether markedly differs from the established behavior in solution.

Tailoring the volatility and stability of oligopeptides.

Amino acids are essential building blocks of life, and fluorinated derivatives have gained interest in chemistry and medicine. Modern mass spectrometry has enabled the study of oligo- and polypeptides as isolated entities in the gas phase, but predominantly as singly or even multiply charged species. While laser desorption of neutral peptides into adiabatically expanding supersonic noble gas jets is possible, UV-VIS spectroscopy, electric or magnetic deflectometry as well as quantum interferometry would profit from the possibility to prepare thermally slow molecular beams. This has typically been precluded by the fragility of the peptide bond and the fact that a peptide would rather 'fry', i.e. denature and fragment than 'fly'. Here, we explore how tailored perfluoroalkyl functionalization can reduce the intermolecular binding and thus increase the volatility of peptides and compare it to previously explored methylation, acylation and amidation of peptides. We show that this strategy is essential and enables the formation of thermal beams of intact neutral tripeptides, whereas only fragments were observed for an extensively fluoroalkyl-decorated nonapeptide. © 2017 The Authors. Journal of Mass Spectrometry Published by John Wiley & Sons Ltd.

Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes.

Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d(6)-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction.

First domino mukaiyama-aldol cyclizations of 1, 3-Bis(trimethylsiloxy)-1,3-butadienes with 1,2-diketones

The first domino Mukaiyama-aldol cyclization of 1, 3-bis(trimethylsiloxy)-1,3-dienes with enolizable 1,2-diketones provides a convenient and regioselective access to substituted cyclopent-2-en-1-ones.

[Cryotherapy as analgesic technique in direct, postoperative treatment following elective joint replacement]. / Kryotherapie als Analgesietechnik in der direkten, postoperativen Behandlung nach elektivem Gelenkersatz.

The application of crushed ice or hydrogenated silicate, a micro-crystalline substitute has been used as a method to treat posttraumatic and postoperative irritations of the locomotor system for a long time. Closed systems using pumps can be viewed as further development as they enable continuous, water-free cooling of operating areas. The analgetic effect of postoperative cold therapy was evaluated in a prospective clinical trial, including 312 patients after total knee or hip arthroplasty. Conventional cold packs, consisting of microcrystalline silicate were compared to a continuous applicable closed system. Continuous cryotherapy resulted in a depression of skin temperature to 12 degrees C, whereas intermittent cooling only caused a mean temperature decrease of 1 degree C. Clinically continuous cold application leads to a more than 50% decrease of analgetic demands in both, systemic and regional application (p < 0.001). This observation was found in a significant correlation with patient's pain sensation as well as primary range of motion. Intermittent cryotherapy was found to be ineffective in postoperative pain relieve in hip- and adequate in knee arthroplasty patients. We could not report an influence on postoperative blood loss, as discussed in previous reports.

Time course of locomotor recovery and functional regeneration in spinal-transected lamprey: kinematics and electromyography.

The time course of recovery of locomotor function was examined with kinematic analysis and muscle recordings in larval lampreys 2-32 weeks after rostral spinal cord transection at the level of the third gill (approximately 10% of body length, BL). Animals began to recover locomotor movements within 2-4 weeks of spinal cord transection, but the amplitude of locomotor movements in the tail region was less than in normal animals. At 2 weeks post-transection, locomotor activity was limited to 20% BL, and at 3 weeks after spinal transection activity could be recorded at least as far as 40% BL. At 4 weeks after spinal transection, well-coordinated locomotor muscle activity was often present as far as 60% BL. At 8 weeks of recovery and longer, well-coordinated locomotor activity was present consistently at least as far as 60% BL, and the amplitudes of locomotor movements were restored to normal values. At each recovery time examined the ranges of locomotor parameters (cycle time, burst proportion, and intersegmental phase lag) overlapped with those in normal animals. Thus, the gradual recovery of the amplitude of locomotor movements in the caudal body is associated with the gradual return of coordinated muscle activity at progressively more caudal levels along the body. The mechanisms responsible for this gradual recovery of locomotor function are discussed in relation to our recent anatomical and in vitro studies.

Macrophage-bound C3 fragments as adhesion molecules modulate presentation of exogenous antigens.

The involvement of complement in the response to T cell dependent antigens is generally accepted, however the mechanism has not been clarified. We compared the T cell response in vitro, using antigen-pulsed macrophages from normal and genetically C3-deficient guinea pigs, and show, that C3-fragments fixed covalently to the surface of the antigen-presenting cells are involved in the triggering of responder T cells. Binding of guinea pig C3-specific mAb to oil-elicited, OVA- and PPD-pulsed macrophages of C3D guinea pigs is reduced compared to normal cells, while the expression of Ia antigens is the same. C3-like peptides can be immunoprecipitated only from the lysate of oil-elicited normal cells. These C3-fragments are fixed to the cell-membrane via ester-bonds, since they are released upon treatment with hydroxylamine. In comparison with normal cells, the antigen-presenting capacity of macrophages derived from C3D animals is strongly impaired in cultures containing 10% normal guinea pig serum. A further impairment is observed in cultures with 10% C3D guinea pig serum. Two of the tested C3-specific mAb inhibited antigen-induced T cell proliferation in a dose-dependent manner. Our data point to the importance of C3, as a bivalent molecule, having the capacity to facilitate the cooperation between the antigen-presenting cell and the responder T lymphocytes.

[Adamantinoma of the fibula--follow-up study]. / Ein Adamantinom der Fibula--Verlaufskontrolle.

A case of the adamantinom of the fibula has been reported. The tumor was resected six years ago. The yearly follow-up showed no sign of a relapse or metastases.

[Results of a long-term study of arteriosclerotic circulatory disorders with polyene fatty acid therapy]. / Ergebnisse einer Langzeitstudie arteriosklerotischer Durchblutungsstörungen unter Polyenfettsäurentherapie.

The antiatherogenic oil diet as one factor of therapy causes the hope of favourable effects in the complex primary prophylaxis. By means of this alone, however, a regression of a clinically significant arteriosclerosis cannot be achieved within 3 years, through biochemically unequivocal "antiatherogenic" effects are to be proved. Linseed-oil, fish and fish oil seem to be particularly suited to cause these effects desired.

[The aged person as patient (author's transl)]. / Der gealterte Mensch als Patient.

Old people with diminished vigilance show a reduced serum-beta-glucuronidase activity. This means insufficiency of impulse, adaptation, regeneration; sometimes decrease of the dominant gene pattern with consecutive depression. Is the disorder of the "basic physical and psychological condition" a symptom of a physiophysical call lability?

Helpful hints for measuring pH.

Although pH is probably one of the most common laboratory measurements, it often is one of the most troublesome. Frequently the trouble arises because of improper care of the electrodes. Considered here are several common problems and suggestions for solving or avoiding them.