Mass spectrometry analysis for the determination of side reactions for cyclic peptides prepared from an Fmoc/t}Bu/Dmab protecting group strategy

Summary The Association of Biomolecular Resource Facilities (ABRF) Peptide Synthesis Research Group (PSRG) proposed for their annual study that laboratory members preparecyclo(Tyr-Glu-Ala-Ala-Arg-DPhe-Pro-Glu-Asp-Asn) according to the following synthetic pathway: (i) side-chain anchoring Fmoc-Asp(OH)-ODmab to a Rink amide resin; (ii) linear assembly; (iii) Dmab and Fmoc removal, respectively; (iv) on-resin cyclization with an uronium-based coupling reagent; (v) final cleavage/deprotection with TFA. Based upon this protocol, a variety of side-products were identified: (i)N-terminal guanidine formation; (ii)C-terminal piperidyl amide formation; and (iii) a novelC-terminal benzyl amide-guanidine derivative that formed due to a chemical reaction between the Dmab protecting group and the uronium-based coupling agent. The elemental composition and subsequent structure determination of this unexpected derivative was established by tandem mass spectrometry, i.e. low energy collision-induced dissociation experiments with fragment mass determination within 5 ppm.     

Nanostructured Antimicrobials in Food Packaging—Recent Advances

Active food packaging systems promote better food quality and/or stability, such as by releasing antimicrobial agents into food. Advantages of adding antimicrobials to the packaging material instead of into the bulk food include controlled diffusion, reduced antimicrobial contents, and improved cost effectiveness. Nanostructured antimicrobials are especially effective due to their high specific surface area. The present review is focused on recent advances and findings on the main nanostructured antimicrobial packaging systems for food packaging purposes. Several kinds of nanostructures, including both inorganic particles and organic structures, have been proven effective antimicrobials by different mechanisms of action and with different application scopes. Moreover, there are systems containing nanocarriers to protect antimicrobials and deliver them in a controlled fashion. On the other hand, scientific data about migration of nanostructures onto food and their toxicity are still limited, requiring special attention from researchers and regulation sectors.     

Regulation of GPCR signaling in Hypertension

Hypertension represents a complex, multifactorial disease and contributes to the major causes of morbidity and mortality in industrialized countries: ischemic and hypertensive heart disease, stroke, peripheral atherosclerosis and renal failure. Current pharmacological therapy of essential hypertension focuses on the regulation of vascular resistance by inhibition of hormones such as catecholamines and angiotensin II, blocking them from receptor activation. Interaction of G-protein coupled receptor kinases (GRKs) and regulator of G-protein signaling (RGS) proteins with activated G-protein coupled receptors (GPCRs) effect the phosphorylation state of the receptor leading to desensitization and can profoundly impair signaling. Defects in GPCR regulation via these modulators have severe consequences affecting GPCR-stimulated biological responses in pathological situations such as hypertension, since they fine-tune and balance the major transmitters of vessel constriction versus dilatation, thus representing valuable new targets for anti-hypertensive therapeutic strategies. Elevated levels of GRKs are associated with human hypertensive disease and are relevant modulators of blood pressure in animal models of hypertension. This implies therapeutic perspective in a disease that has a prevalence of 65 million in the United States while being directly correlated with occurrence of major adverse cardiac and vascular events. Therefore, therapeutic approaches using the inhibition of GRKs to regulate GPCRs are intriguing novel targets for treatment of hypertension and heart failure.     

Parameters of ragweed pollination in the Lyon’s area (France) from 14 years of pollen counts

This study analyzes the pollen counts obtained from the air of the greater Lyon (corresponding to the urban area of Lyon) an area which has been overrun by ragweed in the last 40 years. Two periods are investigated, 1982–1989 and 1990–1995. The year 1995 deserves specific attention because for the first time a campaign of ragweed eradication was launched in greater Lyon. From the data of the 14 pollination seasons it was possible to define some parameters: subpathological risk period, pathological risk period and the position and level of the pollen peak. Our study indicates the progression of the weed in the infested area over the two periods. In 1995 a slight decrease in the pollen count was observed but this was followed by a second peak probably related to later growth of some plants which had been cut. In this connection, 4 weeks weeding campaign is not long enough and in the future a 6-week campaign without the use of weedkillers should be planned. Determining the parameters of ragweed pollination every year will be useful both to patients and physicians concerned by allergy to ragweed pollen. According to the level of the ragweed pollen in the air, the patients may take appropriate medication. This study emphasizes the necessity to record air pollen concentrations over many years. In particular, the actual impact of cutting ragweed before pollination on ragweed pollen counts can only be evaluated after several years of eradication.