Hydrocarbon Stapled Antimicrobial Peptides

Antimicrobial peptides are promising candidates for anti-infective pharmaceuticals. Unfortunately, because of their low proteolytic and chemical stability, their usage is generally narrowed down to topical formulations. Until now, numerous approaches to increase peptide stability have been proposed. One of them, peptide hydrocarbon stapling, a modification based on stabilizing peptide secondary structure with a side-chain covalent hydrocarbon bridge, have been successfully applied to many peptides. Moreover, constraining secondary structure of peptides have also been proven to increase their biological activity. This review article describes studies on hydrocarbon stapled antimicrobial peptides with respect to improved drug-like properties.     

Assessment of gestation,lactation and fasting on stable isotope ratios in northern elephant seals (Mirounga angustirostris)

Effects of physiological processes such as gestation, lactation and nutritional stress on stable isotope ratios remain poorly understood. To determine their impact, we investigated these processes in simultaneously fasting and lactating northern elephant seals (Mirounga angustirostris). Stable carbon and nitrogen isotope values were measured in blood and milk of 10 mother-pup pairs on days 5 and 22 of lactation. As long- and short-term integrators of diet, blood cells and serum may reflect foraging data or energy reserves from late gestation and lactation, respectively. Limited changes in isotopic signatures of maternal blood over the lactating period were highlighted. Nitrogen isotope fractionation associated with mother-to-offspring transfer of nutrients was generated between mother and offspring during gestation and lactation. This fractionation was tissue and time-specific, it varied between early and late lactation from +0.6‰ to +1.3‰ in blood cells and from +1.1‰ to nonsignificant value in serum. Therefore, if pups appear to be good proxies to investigate the female trophic ecology especially for C sources, much more caution is required in using δ¹⁵N values. Further studies are also needed to better define the relative impact of fasting and lactation on the enrichment or depletion of isotopes in different tissues.     

Influence of breathing pattern on oxygen exchange during hypoxia and exercise.

During hypoxia, arterial oxygen saturation (SaO2) measured by ear oximeter shows cyclic fluctuations which are related to the pattern and rate of breathing. Continuous recordings of SaO2 may be corrected for distortion, due to circulatory transport, to yield approximate values for pulmonary end-capillary saturation (Sc'O2). This permits calculation of the corresponding end-capillary PO2 (Pc'O2). We have used this technique to study the effect of spontaneous and imposed breathing patterns on mean Pc'O2, amplitude of Pc'O2 (delta Pc'O2) and minute ventilation (VE). The studies were conducted during mild hypoxia, at rest and exercise. The amplitude of delta Pc'O2 is inversely related to breathing frequency. When frequency is constant, patterns with with prolonged expiration or end-expiratory pauses produce large delta Pc'O2 and greater VE. This effect is reversed with prolonged inspiration or end-inspiratory pauses. Spontaneous breathing patterns produced smaller delta Pc'O2, with lower VE than imposed patterns. These findings are compatible with animal studies which suggest the magnitude of PaO2 fluctuations produced by the breathing pattern may act as a feedback stimulus to ventilation. The breathing patterns, which are spontaneously chosen, produce the minimum delta Pc'O2 and VE.