scholarly journals Presence of short and cyclic peptides in Acacia and Ziziphus honeys may potentiate their medicinal values

2021 ◽  
Vol 19 (1) ◽  
pp. 1171-1182
Author(s):  
Wed Mohammed Ali ALaerjani ◽  
Saraa Abdullah Abu-Melha ◽  
Khalid Ali Khan ◽  
Hamed A. Ghramh ◽  
Ali Yahya A. Alalmie ◽  
...  

Abstract Acacia honey is characterized by high nutritional, antioxidant, antibacterial and immuno-modulatory values. This work investigated the presence of short and cyclic peptides in Acacia and Ziziphus honey samples. Acacia honey samples (Acacia tortilis and Acacia hamulosa) and three Ziziphus honeys (Ziziphus spina-christi) were screened for their short and cyclic peptide contents using the LC-MS and the chemical structure databases. Moreover, the total protein content was determined using the Bradford method. The A. tortilis honey contained three short peptides; HWCC, DSST, and ECH, and the A. hamulosa honey sample contained five short peptides and one cyclic peptide. The short peptides of the A. hamulosa honey were Ac-GMGHG-OH (Ac-MGGHG-OH), Boc-R(Aloc)2-C(Pal)-OH, H-C (1)-NEt2·H-C (1)-NEt2, APAP (AAPP), and GAFQ (deamino-2-pyrid-4-yl-glycyl-dl-alanyl-dl-norvalyl-dl-asparagine). The cyclic peptide of the A. hamulosa honey was cyclo[Aad-RGD-d-F] (cyclo[Aad-Arg-Gly-Asp-d-Phe]). The Ziziphus honey was characterized by the presence of either Almiramide B or Auristatin-6-AQ. A. tortilis, A. hamulosa, and Ziziphus honeys are characterized by the presence of short and cyclic peptides which may contribute to their medicinal values.

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt

<p>NOTE: This preprint has been retracted by consensus from all authors. See the retraction notice in place above; the original text can be found under "Version 1", accessible from the version selector above.</p><p><br></p><p>------------------------------------------------------------------------</p><p><br></p><p>Peptides, together with antibodies, are among the most potent biochemical tools to modulate challenging protein-protein interactions. However, current structure-based methods are largely limited to natural peptides and are not suitable for designing target-specific binders with improved pharmaceutical properties, such as macrocyclic peptides. Here we report a general framework that leverages the computational power of Rosetta for large-scale backbone sampling and energy scoring, followed by side-chain composition, to design heterochiral cyclic peptides that bind to a protein surface of interest. To showcase the applicability of our approach, we identified two peptides (PD-<i>i</i>3 and PD-<i>i</i>6) that target PD-1, a key immune checkpoint, and work as protein ligand decoys. A comprehensive biophysical evaluation confirmed their binding mechanism to PD-1 and their inhibitory effect on the PD-1/PD-L1 interaction. Finally, elucidation of their solution structures by NMR served as validation of our <i>de novo </i>design approach. We anticipate that our results will provide a general framework for designing target-specific drug-like peptides.<i></i></p>


Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 268
Author(s):  
Kosuke Saito ◽  
Kotaro Hattori ◽  
Shinsuke Hidese ◽  
Daimei Sasayama ◽  
Tomoko Miyakawa ◽  
...  

Lipidomics provides an overview of lipid profiles in biological systems. Although blood is commonly used for lipid profiling, cerebrospinal fluid (CSF) is more suitable for exploring lipid homeostasis in brain diseases. However, whether an individual’s background affects the CSF lipid profile remains unclear, and the association between CSF and plasma lipid profiles in heathy individuals has not yet been defined. Herein, lipidomics approaches were employed to analyze CSF and plasma samples obtained from 114 healthy Japanese subjects. Results showed that the global lipid profiles differed significantly between CSF and plasma, with only 13 of 114 lipids found to be significantly correlated between the two matrices. Additionally, the CSF total protein content was the primary factor associated with CSF lipids. In the CSF, the levels of major lipids, namely, phosphatidylcholines, sphingomyelins, and cholesterolesters, correlated with CSF total protein levels. These findings indicate that CSF lipidomics can be applied to explore changes in lipid homeostasis in patients with brain diseases.


2005 ◽  
Vol 33 (3) ◽  
pp. 207-213 ◽  
Author(s):  
Paul J. Dierickx

In our previously described Hep G2/24-hour/total protein assay, protein levels were measured by using the Lowry method. This assay was the best acute in vitro assay for the prediction of human toxicity within the Multicentre Evaluation of In Vitro Cytotoxicity (MEIC) study. In order to increase the MEIC data-base with a wider range of chemicals, we were interested in introducing the more practical 3-(4-carboxybenzoyl)-quinoline-2-carboxaldehyde (CBQCA) method for the quantification of the total protein content. Therefore, we investigated whether the same good results for the prediction of acute human toxicity would be obtained with the CBQCA method. The cells were treated for 24 hours, then cytotoxicity was determined by measuring the total protein content with CBQCA. The results were quantified by using the PI50c: the concentration (in mM) of test compound required to reduce the total protein content measured with the CBQCA-method by 50% as compared to the control cells. The results were compared with the PI50, the corresponding value when the Lowry method was used. A relatively low correlation was observed between PI50 and PI50c, reflecting the large and unexpected, differences when using the two protein assays. However, when comparing the log PI50c with the human toxicity, a correlation coefficient of r2 = 0.761 ( n = 44) was obtained for exactly the same series of MEIC chemicals. This value is clearly higher than that for the Lowry method ( r2 = 0.695). Compared to the Lowry method originally used, the Hep G2/24-hour/CBQCA total protein assay has the additional important advantage that it can be very easily adapted for large-scale analyses with robotic systems, including the on-line calculation of the results.


Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 311
Author(s):  
Yang Li ◽  
Wang Li ◽  
Zhengshuang Xu

Peptides have a three-dimensional configuration that can adopt particular conformations for binding to proteins, which are well suited to interact with larger contact surface areas on target proteins. However, low cell permeability is a major challenge in the development of peptide-related drugs. In recent years, backbone N-methylation has been a useful tool for manipulating the permeability of cyclic peptides/peptidomimetics. Backbone N-methylation permits the adjustment of molecule’s conformational space. Several pathways are involved in the drug absorption pathway; the relative importance of each N-methylation to total permeation is likely to differ with intrinsic properties of cyclic peptide/peptidomimetic. Recent studies on the permeability of cyclic peptides/peptidomimetics using the backbone N-methylation strategy and synthetic methodologies will be presented in this review.


Author(s):  
J.G. Thompson ◽  
A.N.M. Sherman ◽  
N.W. Allen ◽  
L.T. McGowan ◽  
H.R. Tervit

2021 ◽  
Vol 7 (3) ◽  
pp. 204
Author(s):  
Shengwen Zhou ◽  
Xincan Li ◽  
Yunjiao Lüli ◽  
Xuan Li ◽  
Zuo H. Chen ◽  
...  

Most species in the genus Amanita are ectomycorrhizal fungi comprising both edible and poisonous mushrooms. Some species produce potent cyclic peptide toxins, such as α-amanitin, which places them among the deadliest organisms known to mankind. These toxins and related cyclic peptides are encoded by genes of the “MSDIN” family (named after the first five amino acid residues of the precursor peptides), and it is largely unknown to what extent these genes are expressed in the basidiocarps. In the present study, Amanita rimosa and Amanita exitialis were sequenced through the PacBio and Illumina techniques. Together with our two previously sequenced genomes, Amanita subjunquillea and Amanita pallidorosea, in total, 46 previously unknown MSDIN genes were discovered. The expression of over 80% of the MSDIN genes was demonstrated in A. subjunquillea. Through a combination of genomics and mass spectrometry, 12 MSDIN genes were shown to produce novel cyclic peptides. To further confirm the results, three of the cyclic peptides were chemically synthesized. The tandem mass spectrometry (MS/MS) spectra of the natural and the synthetic peptides shared a majority of the fragment ions, demonstrating an identical structure between each peptide pair. Collectively, the results suggested that the genome-guided approach is reliable for identifying novel cyclic peptides in Amanita species and that there is a large peptide reservoir in these mushrooms.


Author(s):  
D. Skafar ◽  
D. Shumeyko

Purpose: to study the effect of ethanol on the parameters of THC, the percentage of granulocytes and total protein in the hemolymph of the Red claw crayfish (Cherax quadricarinatus).Materials and methods. The object of this experiment was 26 males of the Australian red-clawed crayfish (Cherax quadricarinatus) weighing from 23 to 83 g. The individuals were evenly divided into two experimental groups - with an injection of ethanol and a control group without an injection of 13 crayfish for each group. The injection dose was 2515 mg per 100 g of body weight. A day after the introduction of ethanol, hemolymph was taken with a syringe from the ventral sinus, the syringe was pre-washed with a 4% EDTA-Na2 solution. Three parameters were determined: the total hemocyte count (THC), percent granulocytes and percent total protein content. Counting of hemocytes and determination of granulocytes were performed in a Goryaev chamber under a light microscope. The total protein was determined by the refractometric method.Results. Differences in THC and total protein between the groups were statistically unreliable (p>0,05). THC in the experimental group is 36% more than in the control group. The total protein after the introduction of ethanol actually increased by 0,7%, and relatively by 14%. There were statistically different indicators of the proportion of granulocytes (p<0,05) - the average value of 33,1% in the experimental group versus 24,5% in the control group. A reliable (p<0,05) strong feedback was revealed between the total protein and the mass of individuals in both experimental groups, while in the experimental group there is a visible shift in the values of dependent hemolymph indicators towards an increase in smaller individuals.Conclusion. A single injection of ethyl alcohol with a dosage of 2515 mg per 100 g of body weight into the hemolymph of C. quadricarinatus does not cause significant changes in the THC and total protein after 24 hours. At the same time, the proportion of granulocytes actually increases by 9%, relative to 37%. This may indicate that granulocytes are involved in the formation of cancer defense mechanisms when exposed to toxic substances. The effect of different dosages of ethanol injections and the duration of its effect on hematological parameters requires additional consideration. It is necessary to investigate its effect on other indicators, such as the pH and buffer capacity of the hemolymph, the concentration of hemocyanin, glucose, lactates and calcium.


2002 ◽  
Vol 16 (3) ◽  
pp. 209-215 ◽  
Author(s):  
Adalberto Luiz Rosa ◽  
Márcio Mateus Beloti ◽  
Richard van Noort ◽  
Paul Vincent Hatton ◽  
Anne Jane Devlin

Hydroxyapatite (HA) has been used in orthopedic, dental, and maxillofacial surgery as a bone substitute. The aim of this investigation was to study the effect of surface topography produced by the presence of microporosity on cell response, evaluating: cell attachment, cell morphology, cell proliferation, total protein content, and alkaline phosphatase (ALP) activity. HA discs with different percentages of microporosity (< 5%, 15%, and 30%) were confected by means of the combination of uniaxial powder pressing and different sintering conditions. ROS17/2.8 cells were cultured on HA discs. For the evaluation of attachment, cells were cultured for two hours. Cell morphology was evaluated after seven days. After seven and fourteen days, cell proliferation, total protein content, and ALP activity were measured. Data were compared by means of ANOVA and Duncan’s multiple range test, when appropriate. Cell attachment (p = 0.11) and total protein content (p = 0.31) were not affected by surface topography. Proliferation after 7 and 14 days (p = 0.0007 and p = 0.003, respectively), and ALP activity (p = 0.0007) were both significantly decreased by the most irregular surface (HA30). These results suggest that initial cell events were not affected by surface topography, while surfaces with more regular topography, as those present in HA with 15% or less of microporosity, favored intermediary and final events such as cell proliferation and ALP activity.


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