scholarly journals Modifications of the acyl-d-alanyl-d-alanine terminus affecting complex-formation with vancomycin

1971 ◽  
Vol 123 (5) ◽  
pp. 789-803 ◽  
Author(s):  
M. Nieto ◽  
H. R. Perkins

Vancomycin forms complexes with peptides terminating in d-alanyl-d-alanine that are analogous to the biosynthetic precursors of bacterial mucopeptides. The specificity of complex-formation has been studied by means of many synthetic peptides, prepared by both solid-phase and conventional methods. The following conclusions can be drawn: (a) three amide linkages are required to form a stable complex; (b) the terminal carboxyl group must be free; (c) the carboxyl terminal and subterminal residues must be either glycine or of the d-configuration; (d) the size of the side chain in these residues greatly influences the affinity for vancomycin, a methyl group being the optimum in each case; (e) the nature of the side chain in the third and fourth residues has a smaller effect on complex-formation, but an l-configuration was somewhat better than a d-configuration in the third position. In addition to acyl-d-alanyl-d-alanine, other peptides that occur in bacterial cell walls will combine with vancomycin, although less strongly, e.g. acyl-d-alanyl-d-α-amino acid (where the terminal d-residue may form the cross-link in mucopeptide structure) and acyl-l-alanyl-d-glutamylglycine (a sequence found in the mucopeptide of Micrococcus lysodeikticus and related organisms). These results throw some light on the specificity of the uptake of vancomycin by living bacteria.

1968 ◽  
Vol 11 (4) ◽  
pp. 825-832 ◽  
Author(s):  
Marilyn M. Corlew

Two experiments investigated the information conveyed by intonation from speaker to listener. A multiple-choice test was devised to test the ability of 48 adults to recognize and label intonation when it was separated from all other meaning. Nine intonation contours whose labels were most agreed upon by adults were each matched with two English sentences (one with appropriate and one with inappropriate intonation and semantic content) to make a matching-test for children. The matching-test was tape-recorded and given to children in the first, third, and fifth grades (32 subjects in each grade). The first-grade children matched the intonations with significantly greater agreement than chance; but they agreed upon significantly fewer sentences than either the third or fifth graders. Some intonation contours were matched with significantly greater frequency than others. The performance of the girls was better than that of the boys on an impatient question and a simple command which indicates that there was a significant interaction between sex and intonation.


1990 ◽  
Vol 29 (03) ◽  
pp. 167-181 ◽  
Author(s):  
G. Hripcsak

AbstractA connectionist model for decision support was constructed out of several back-propagation modules. Manifestations serve as input to the model; they may be real-valued, and the confidence in their measurement may be specified. The model produces as its output the posterior probability of disease. The model was trained on 1,000 cases taken from a simulated underlying population with three conditionally independent manifestations. The first manifestation had a linear relationship between value and posterior probability of disease, the second had a stepped relationship, and the third was normally distributed. An independent test set of 30,000 cases showed that the model was better able to estimate the posterior probability of disease (the standard deviation of residuals was 0.046, with a 95% confidence interval of 0.046-0.047) than a model constructed using logistic regression (with a standard deviation of residuals of 0.062, with a 95% confidence interval of 0.062-0.063). The model fitted the normal and stepped manifestations better than the linear one. It accommodated intermediate levels of confidence well.


1994 ◽  
Vol 59 (6) ◽  
pp. 1439-1450 ◽  
Author(s):  
Miroslava Žertová ◽  
Jiřina Slaninová ◽  
Zdenko Procházka

An analysis of the uterotonic potencies of all analogs having substituted L- or D-tyrosine or -phenylalanine in position 2 and L-arginine, D-arginine or D-homoarginine in position 8 was made. The series of analogs already published was completed by the solid phase synthesis of ten new analogs having L- or D-Phe, L- or D-Phe(2-Et), L- or D-Phe(2,4,6-triMe) or D-Tyr(Me) in position 2 and either L- or D-arginine in position 8. All newly synthesized analogs were found to be uterotonic inhibitors. Deamination increases both the agonistic and antagonistic potency. In the case of phenylalanine analogs the change of configuration from L to D in position 2 enhances the uterotonic inhibition for more than 1 order of magnitude. The L to D change in position 8 enhances the inhibitory potency negligibly. Prolongation of the side chain of the D-basic amino acid in position 8 seems to decrease slightly the inhibitory potency if there is L-substituted amino acid in position 2. On the other hand there is a tendency to the increase of the inhibitory potency if there is D-substituted amino acid in position 2.


In the years since the publication of Atherton and Sheppard's volume, the technique of Fmoc solid-phase peptide synthesis has matured considerably and is now the standard approach for the routine production of peptides. The basic problems outstanding at the time of publication of this earlier work have now been, for the most part, solved. As a result, innovators in the field have focussed their efforts to develop methodologies and chemistry for the synthesis of more complex structures. The focus of this new volume is much broader, and covers not only the essential procedures for the production of linear peptides but also more advanced techniques for preparing cyclic, side-chain modified, phospho- and glycopeptides. Many other methods also deserving attention have been included: convergent peptide synthesis; peptide-protein conjugation; chemoselective ligation; and chemoselective purification. The difficult preparation of cysteine and methionine-containing peptides is also covered, as well as methods for overcoming aggregation during peptide chain assembly and a survey of available automated instrumentation.


Author(s):  
Dong-mei Yin ◽  
Philip de Groot ◽  
Marisa Ninivaggi ◽  
Katrien M.J. Devreese ◽  
Bas de Laat

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098284
Author(s):  
Tingting Qiao ◽  
Simin Liu ◽  
Zhijun Cui ◽  
Xiaqing Yu ◽  
Haidong Cai ◽  
...  

Objective To construct deep learning (DL) models to improve the accuracy and efficiency of thyroid disease diagnosis by thyroid scintigraphy. Methods We constructed DL models with AlexNet, VGGNet, and ResNet. The models were trained separately with transfer learning. We measured each model’s performance with six indicators: recall, precision, negative predictive value (NPV), specificity, accuracy, and F1-score. We also compared the diagnostic performances of first- and third-year nuclear medicine (NM) residents with assistance from the best-performing DL-based model. The Kappa coefficient and average classification time of each model were compared with those of two NM residents. Results The recall, precision, NPV, specificity, accuracy, and F1-score of the three models ranged from 73.33% to 97.00%. The Kappa coefficient of all three models was >0.710. All models performed better than the first-year NM resident but not as well as the third-year NM resident in terms of diagnostic ability. However, the ResNet model provided “diagnostic assistance” to the NM residents. The models provided results at speeds 400 to 600 times faster than the NM residents. Conclusion DL-based models perform well in diagnostic assessment by thyroid scintigraphy. These models may serve as tools for NM residents in the diagnosis of Graves’ disease and subacute thyroiditis.


2021 ◽  
Vol 67 (1) ◽  
Author(s):  
Shirong Sun ◽  
Tomoya Yokoyama

AbstractMonomeric C6-C2-type lignin model compounds with a p-hydroxyphenyl (H), guaiacyl (G), syringyl (S), or p-ethylphenyl (E) nucleus (1-phenylethanol derivatives) were individually oxidized by MnO2 at a pH of 1.5 and room temperature. The results were compared with those of the corresponding C6-C1-type benzyl alcohol derivatives obtained in our recent report to examine the effect of the presence of the β-methyl group on the oxidation. The presence decelerated the oxidation regardless of the type of aromatic nucleus, although it did not change the order of the oxidation rates: G > S >> H > E. This deceleration results from the steric factor of the β-methyl group in the C6-C2-type compounds. The MnO2 oxidations of the corresponding C6-C2-type compounds deuterated at their α-(benzyl)positions showed that the magnitudes of the kinetic isotope effects are smaller than those observed in the oxidations of the corresponding C6-C1-type compounds, regardless of the type of aromatic nucleus. These smaller magnitudes suggest that the presence of the β-methyl group shifts the initial oxidation mode of MnO2 from direct oxidation of the benzyl position to one-electron oxidation of the aromatic nucleus. Only the S-type compounds afforded products via degradation of the aromatic nuclei.


1979 ◽  
Vol 44 (4) ◽  
pp. 1173-1178 ◽  
Author(s):  
Viktor Krchňák ◽  
Milan Zaoral

A series of solid-phase syntheses of the protected precursor II of DDAVP was carried out. Experimental conditions were developed under which practically pure II can reproducibly be obtained in yields better than 60%. The protected precursors of DDAVP obtained by liquid- and solid-phase synthesis and DDAVP samples obtained from these precursors were undistinguishable by conventional analytical or pharmacological assays.


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