SumnaryThe structure and absolute configuration of antibiotic X-537A have been determined by physical and chemical methods.~~ THE isolation of three crystalline antibiotics, X-206, X-464, and X-53'iA from three different Streptomyces species was reported from this laboratoryt in 1951. The three antibiotics had similar biological activity as well as the unusual property that their alkali salts were soluble in such nonpolar solvents as benzene and ether, but virtually insoluble in water. Antibiotic X-464 has recently been shown2 to be identical to nigericin, (polyetherin A4) using a combination of i.r., mass spectral, and polarimetric methods. Nigericin belongs to the same class of polyether antibiotics as the m~nensins.~ These compounds have the common property of being monocarboxylic acids containing a number of cyclic ether moieties.Antibiotic X-537A (C34H~408)~ m.p. 110-1 14", [a]:-7.55" (c 1, MeOH) was unique in this class of antibiotics in possessing an aromatic chromophore with U.V. maxima at 248 ( E 6750) and 318nm (E 4200) in 50% aqueous isopropyl alcohol. The sodium salt (C34H5308Na) m.p. l68-l7l0, [a]L5 -30" (G 1, MeOH) had an inflection in the U.V. a t 245 and a maximum at 308nm (E 4100). The presence of a phenolic group was indicated by a positive iron( 111) chloride reaction' in chloroform suggesting that the chromophore was a hydroxybenzoic acid. Both m-and p-hydroxybenzoic acids gave negative iron ( I I I) chloride reactions whereas salicylic acid gave an identical reaction to the antibiotic. Potentiometric titration in 66% dimethylforrnamide gave a single pka = 5.13 (salicylic acid = 4-55, $72-hydroxybenzoic acid = 6.8, 12.9). Further proof of a salicylic chromophore for the antibiotic was the hypsochromic shift in the U.V. on transformation of the free acid to its salt form. Salicylic acid behaves similarly, but wz-hydroxybenzoic acid undergoes a bathochromic shift under these conditions. N.m.r. (CDCl,) of the barium salt showed the presence of an aromatic methyl singlet a t 8 2.14, and two aromatic protons at 8 6.38 and 6.91 (Jortho 8 Hz).
Background. The E484K and L452R amino acid substitutions on the spike protein of SARS-CoV-2 are associated with reduced neutralization by antibodies from acquired immunity. This study examines the respective association of these mutations with infection in persons who had previously received a COVID-19 vaccine. Methods. Genetic sequences from SARS-CoV-2 specimens collected from Maryland residents and reported to Maryland Department of Health were linked to vaccination history. The prevalence of infections in fully vaccinated persons -- defined as being at least two weeks past receiving the final scheduled dose of a COVID-19 vaccine series -- was compared between infections caused by viruses carrying E484K to those not carrying E484K, and between infections caused by viruses carrying L452R to those not carrying L452R, using logistic regression to adjust for confounding. Results. Of 9,048 sequenced SARS-CoV-2 specimens examined, 265 (2.9%) were collected from fully vaccinated persons. In adjusted analysis, the E484K substitution was associated with an increase in the odds of the sequenced specimen being collected from a fully vaccinated person (OR 1.96, 95% CI, 1.36 to 2.83). The L452R mutation was not significantly associated with infections in vaccinated persons (OR 1.07, 95% CI, 0.69 to 1.68). Conclusion. Though more than 97% of SARS-CoV-2 infections were in persons who were not fully vaccinated, the E484K mutation was associated with increased odds of SARS-CoV-2 infection in vaccinated persons. Linking vaccination and sequencing data can help identify and estimate the impact SARS-CoV-2 mutations may have on vaccine effectiveness.
During the past ten years there have been numerous experiments which involve the synthesis and characterization of coordination compounds.1 In the main these experiments are performed over two or three lab days. Often titrations, molecular weight and spectral data are used to elucidate the structure of the compound. In an attempt to produce a shorter experiment which employs more techniques, a new experiment was developed. The student is given an unknown coordination complex and asked to identify it, using both chemical and physical data.
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