Sodium trifluoroacetate as a tune/calibration compound for positive- and negative-ion electrospray ionization mass spectrometry in the mass range of 100–4000 Da

We have identified aqueous:acetonitrile solutions of alkali-metal trifluoroacetate compounds as tune/calibration standards for both positive- and negative-ion electrospray ionization mass spectrometry (ESI/MS). Each alkali-metal trifluoroacetate solution in water and acetonitrile (50:50, v/v) yields evenly spaced, singly charged peaks in the mass range of 100–3500 Da. Intense peaks are formed either by infusing the solution using a syringe pump, by infusing the solution into a stream of liquids [such as a high-performance liquid chromatography (HPLC) mobile phase] flowing to the electrospray needle, or by injecting the salt-containing solution into an HPLC mobile phase containing trifluoroacetic acid. The advantages of these compounds include: (i) generation of singly charged ions in both positive and negative ionization modes in the mass range of approximately 100–3500 Da, (ii) formation of evenly spaced peaks with similar intensity across the entire mass range, (iii) the most abundant isotope in each mass cluster is the lowest mass peak (monoisotopic mass), which is free from variation in natural isotope distribution, (iv) commercial availability, (v) they easily dissolve in common liquid chromatography solvents, and (vi) lack of any long-lasting memory effects or background problems.     

Oxyalkylene polymers with alkylsulfonylmethyl side chains: Gas barrier properties

Gas barrier properties of alkylsulfonylmethyl-substituted poly(oxyalkylene)s are discussed. Oxygen permeability coefficients of three methylsulfonylmethyl-substituted poly(oxyalkylene)s, poly[oxy(methylsulfonylmethyl)ethylene] (MSE), poly[oxy(methylsulfonylmethyl)ethylene-co-oxyethylene] (MSEE), and poly[oxy-2,2-bis (methylsulfonylmethyl)trimethylene oxide] (MST) were measured. MSEE, which has the most flexible backbone of the three polymers, had an oxygen permeability coefficient at 30°C of 0.0036 × 10⁻¹³ cm³(STP)·cm/cm²·s·Pa higher than that of MSE, 0.0014 × 10⁻¹³ cm³(STP)·cm/cm²·s·Pa, because the former polymer's T_g was near room temperature. MST with two polar groups per repeat unit and the highest T_g showed the highest oxygen permeability, 0.013 × 10⁻¹³ cm³(STP) · cm/cm²·s·Pa, among the three polymers, probably because steric hindrance between the side chains made the chain packing inefficient. As the side chain length of poly[oxy(alkylsulfonylmethyl)ethylene] increased, T_g and density decreased and the oxygen permeability coefficients increased. The oxygen permeability coefficient of MSE at high humidity (84% relative humidity) was seven times higher than when it was dry because absorbed water lowered its T_g. At 100% relative humidity MSE equilibrated to a T_g of 15°C after 2 weeks. A 50/50 blend of MSE/MST had oxygen barrier properties better than the individual polymers (O₂ permeability coefficient is 0.0007 × 10⁻¹³ cm³(STP)·cm/cm² ·s·Pa), lower than most commercial high barrier polymers. At 100% relative humidity, it equilibrated to a T_g of 42°C, well above room temperature. These are polymer systems with high gas barrier properties under both dry and wet conditions. © 1998 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 36 : 75–83, 1998     

Synthesis and Characterization of Bone Binding Antibiotic-1 (BBA-1), a Novel Antimicrobial for Orthopedic Applications

Osteomyelitis and orthopedic infections are major clinical problems, limited by a lack of antibiotics specialized for such applications. In this paper, we describe the design and synthesis of a novel bone-binding antibiotic (BBA-1) and its subsequent structural and functional characterization. The synthesis of BBA-1 was the result of a two-step chemical conjugation of cationic selective antimicrobial-90 (CSA-90) and the bisphosphonate alendronate (ALN) via a heterobifunctional linker. This was analytically confirmed by HPLC, FT-IR, MS and NMR spectroscopy. BBA-1 showed rapid binding and high affinity to bone mineral in an in vitro hydroxyapatite binding assay. Kirby—Baur assays confirmed that BBA-1 shows a potent antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus comparable to CSA-90. Differentiation of cultured osteoblasts in media supplemented with BBA-1 led to increased alkaline phosphatase expression, which is consistent with the pro-osteogenic activity of CSA-90. Bisphosphonates, such as ALN, are inhibitors of protein prenylation, however, the amine conjugation of ALN to CSA-90 disrupted this activity in an in vitro protein prenylation assay. Overall, these findings support the antimicrobial, bone-binding, and pro-osteogenic activities of BBA-1. The compound and related agents have the potential to ensure lasting activity against osteomyelitis after systemic delivery.     

Ribosomal Incorporation of Aromatic Oligoamides as Peptide Sidechain Appendages

Derivatives of 4‐aminomethyl‐l ‐phenylalanine with aromatic oligoamide foldamers as sidechain appendages were successfully charged on tRNA by means of flexizymes. Their subsequent incorporation both at the C‐terminus of, and within, peptide sequences by the ribosome, was demonstrated. These results expand the registry of chemical structures tolerated by the ribosome to sidechains significantly larger and more structurally defined than previously demonstrated.     

Determination of L-753,037 in human plasma by liquid chromatography/turbo ionspray tandem mass spectrometry.

A liquid chromatographic/turbo ionspray tandem mass spectrometric (LC/MS/MS) method was developed and validated for the determination of L-753,037, a potent endothelin receptor antagonist currently under development for the treatment of cardiovascular diseases, in human plasma. L-753,037 is extracted from 0.5 ml of human plasma using liquid-liquid extraction and analyzed by LC/MS/MS with a turbo ionspray interface. Method validation results showed that this method is very sensitive, reliable, selective and reproducible. L-753,048, an ethoxy analogue of L-753,037, was used as the internal standard. The method has a lower limit of quantitation (LOQ) of 50 pg ml(-1) with a linear calibration range of 0.05-50 ng ml(-1). The intra-day precision and accuracy (n = 5) were measured to be below 10% relative standard deviation (RSD) and between 97.4 and 102.8% of the nominal values, respectively, for all calibration standard concentrations within the calibration curve range. The inter-day precision and accuracy (n = 3 days, 5 replicates per day) were measured to be below 6.5% RSD and between 99.3 and 102.0% of the nominal values, respectively, for all quality control concentrations. The extraction recovery was determined to be approximately 99% on average. The analyte was found to be stable in plasma through three freeze-thaw cycles, for at least 4 h at ambient temperature and for up to 40 days under -20 degrees C freezer storage conditions. The analyte was also shown to be stable for at least 24 h in the reconstitution solution at room temperature and for up to 3 days as a dried extract at 4 degrees C. Additional variations in plasma concentration of the analyte due to the use of different sources of plasma were also evaluated.