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71.
Cosmin Stefan Mocanu Marius Niculaua Gheorghita Zbancioc Violeta Mangalagiu Gabi Drochioiu 《International journal of molecular sciences》2022,23(5)
Our work discusses the investigation of 75 peptide-based drugs with the potential ability to break the β-sheet structures of amyloid-beta peptides from senile plaques. Hence, this study offers a unique insight into the design of neuropeptide-based drugs with β-sheet breaker potential in the amyloid-beta cascade for Alzheimer’s disease (AD). We started with five peptides (15QKLVFF20, 16KLVFF20, 17LVFF20, 16KLVF19 and 15QKLV18), to which 14 different organic acids were attached at the N-terminal. It was necessary to evaluate the physiochemical features of these sequences due to the biological correlation with our proposal. Hence, the preliminary analysis of different pharmacological features provided the necessary data to select the peptides with the best biocompatibility for administration purposes. Our approaches demonstrated that the peptides 17LVFF20, NA-17LVFF20, 16KLVF19 and NA-16KLVF19 (NA-nicotinic acid) have the ability to interfere with fibril formation and hence improve the neuro and cognitive functions. Moreover, the peptide conjugate NA-16KLVF19 possesses attractive pharmacological properties, demonstrated by in silico and in vitro studies. Tandem mass spectrometry showed no fragmentation for the spectra of 16KLVF19. Such important results suggest that under the action of protease, the peptide cleavage does not occur at all. Additionally, circular dichroism confirmed docking simulations and showed that NA-16KLVF19 may improve the β-sheet breaker mechanism, and thus the entanglement process of amyloid-beta peptides can be more effective. 相似文献
72.
Tao Gong Juan Du Shang-Wei Li Hai Huang Xiao-Lang Qi 《International journal of molecular sciences》2022,23(5)
Coridius chinensis belongs to Dinidoridae, Hemiptera. Previous studies have indicated that C. chinensis contains abundant polypeptides with antibacterial and anticancer activities. Antimicrobial peptides (AMPs), as endogenous peptides with immune function, play an indispensable role in the process of biological development and immunity. AMPs have become one of the most potential substitutes for antibiotics due to their small molecular weight and broad-spectrum antimicrobial activity. In this study, a defensin CcDef2 from C. chinensis was characterized based on bioinformatics and functional analyses. The mature peptide of CcDef2 is a typical cationic peptide composed of 43 amino acid residues with five cations, and contains three intramolecular disulfide bonds and a typical cysteine-stabilized αβ motif in defensins. Phylogenetic analysis showed that CcDef2 belongs to the insect defensin family. Analysis of gene expression patterns showed that CcDef2 was expressed throughout developmental stages of C. chinensis with high levels at the nymphal stage and in adult tissues tested with the highest level in the fat body. In addition, the CcDef2 expression was significantly upregulated in adults infected by bacteria. After expressed in Escherichia coli BL21(DE3) and renatured, the recombinant CcDef2 showed a significant antibacterial effect on three kinds of Gram-positive bacteria. These results indicate that CcDef2 is an excellent antibacterial peptide and a highly effective immune effector in the innate immunity of C. chinensis. This study provides a foundation for further understanding the function of CcDef2 and developing new antimicrobial drugs. 相似文献
73.
Natalia V. Pozdniakova Oxana V. Ryabaya Alevtina S. Semkina Vsevolod A. Skribitsky Alexei B. Shevelev 《International journal of molecular sciences》2022,23(6)
Three artificial proteins that bind the gadolinium ion (Gd3+) with tumour-specific ligands were de novo engineered and tested as candidate drugs for binary radiotherapy (BRT) and contrast agents for magnetic resonance imaging (MRI). Gd3+-binding modules were derived from calmodulin. They were joined with elastin-like polypeptide (ELP) repeats from human elastin to form the four-centre Gd3+-binding domain (4MBS-domain) that further was combined with F3 peptide (a ligand of nucleolin, a tumour marker) to form the F3-W4 block. The F3-W4 block was taken alone (E2-13W4 protein), as two repeats (E1-W8) and as three repeats (E1-W12). Each protein was supplemented with three copies of the RGD motif (a ligand of integrin αvβ3) and green fluorescent protein (GFP). In contrast to Magnevist (a Gd-containing contrast agent), the proteins exhibited three to four times higher accumulation in U87MG glioma and A375 melanoma cell lines than in normal fibroblasts. The proteins remained for >24 h in tumours induced by Ca755 adenocarcinoma in C57BL/6 mice. They exhibited stability towards blood proteases and only accumulated in the liver and kidney. The technological advantages of using the engineered proteins as a basis for developing efficient and non-toxic agents for early diagnosis of tumours by MRI as well as part of BRT were demonstrated. 相似文献
74.
Danna Kamstrup Sell Ane Beth Sloth Babak Bakhshinejad Andreas Kjaer 《International journal of molecular sciences》2022,23(6)
The nonspecific enrichment of target-unrelated peptides during biopanning remains a major drawback for phage display technology. The commercial Ph.D.TM-7 phage display library is used extensively for peptide discovery. This library is based on the M13KE vector, which carries the lacZα sequence, leading to the formation of blue plaques on IPTG-X-gal agar plates. In the current study, we report the isolation of a fast-propagating white clone (displaying WSLGYTG peptide) identified through screening against a recombinant protein. Sanger sequencing demonstrated that white plaques are not contamination from environmental M13-like phages, but derive from the library itself. Whole genome sequencing revealed that the white color of the plaques results from a large 827-nucleotide genomic deletion. The phenotypic characterization of propagation capacity through plaque count- and NGS-based competitive propagation assay supported the higher propagation rate of Ph-WSLGYTG clone compared with the library. According to our data, white plaques are likely to arise endogenously in Ph.D. libraries due to mutations in the M13KE genome and should not always be viewed as exogenous contamination. Our findings also led to the conclusion that the deletion observed here might be an ancestral mutation already present in the naïve library, which causes target-unrelated nonspecific enrichment of white clone during biopanning due to propagation advantage. 相似文献
75.
Lorenza Marinaccio Azzurra Stefanucci Giuseppe Scioli Alice Della Valle Gokhan Zengin Angelo Cichelli Adriano Mollica 《International journal of molecular sciences》2022,23(6)
Elastases are a broad group of enzymes involved in the lysis of elastin, the main component of elastic fibres. They are produced and released in the human body, mainly by neutrophils and the pancreas. The imbalance between elastase activity and its endogenous inhibitors can cause different illnesses due to their excessive activity. The main aim of this review is to provide an overview of the latest advancements on the identification, structures and mechanisms of action of peptide human neutrophil elastase inhibitors isolated from natural sources, such as plants, animals, fungi, bacteria and sponges. The discovery of new elastase inhibitors could have a great impact on the pharmaceutical development of novel drugs through the optimization of the natural lead compounds. Bacteria produce mainly cyclic peptides, while animals provide for long and linear amino acid sequences. Despite their diverse natural sources, these elastase inhibitors show remarkable IC50 values in a range from nM to μM values, thus representing an interesting starting point for the further development of potent bioactive compounds on human elastase enzymes. 相似文献
76.
《Advanced functional materials》2018,28(35)
The introduction of a stimulus‐responsive property is an effective way to increase the applicability of functional materials in the field of nanobiotechnology. Herein, a peptide platform is devised for constructing elastin‐like peptide amphiphiles (ELPAs) that exhibit a temperature‐responsiveness that can be easily tuned via a single N‐terminal amino acid substitution at the final step of peptide synthesis. Due to the modular property of peptides, the platform based on a miniaturized elastin‐like peptide (MELP) can be conjugated with various bioactive peptide sequences in diverse macromolecular topologies. First, the MELP platform is coupled with a short linear RGD peptide. The ELPAs of the peptide conjugates exhibit rapid aggregation (coacervation) and retard disaggregation in response to heating and cooling, respectively. Second, the platform is grafted with an α‐helical guest peptide in a lariat‐type structure, which forms ELPAs that undergo faster disassembly than the ELPAs without the guest peptide in response to temperature increases. Interestingly, the critical temperatures for the thermoresponsive behaviors are commonly dependent on the hydrophobic and aromatic properties of the N‐terminal amino acid residues. These results suggest that this peptide platform possesses great potential for use in the development of smart materials in wide‐ranging applications related to temperature change. 相似文献
77.
Yuanming Wu Xiaohua Chen Li Wang Lunjie Wu Lu Lin Wenwu Ding Zhenming Che Jianfeng Wang Jianzhou Li Yi Liu Weifeng Sun 《International Journal of Food Science & Technology》2020,55(4):1825-1832
Preparation of flavour peptides with microorganisms is an attractive choice for its large-scale production. However, beefy meaty peptide (BMP), as a research hotspot in the field of umami peptide, has been studied in few microorganisms, and furthermore, the safe preparation of BMP has not yet been reported. In this study, multi-copy BMP (8BMP) was successfully expressed and produced in the ‘generally recognized as safe’ Bacillus subtilis (B. subtilis). Firstly, 8BMP with the potentially intense umami was screened out based on molecular docking analysis. Then, it was successfully expressed in the B. subtilis 168 and verified through sensory evaluation. Finally, the scaling capacity of 8BMP was evaluated in a 5-L fermenter, with the highest yield (0.84 g L−1) 6.4 times than that of shake flask, which is conductive for industrial production of BMP and other food peptides. 相似文献
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