Current Issue : January - March Volume : 2020 Issue Number : 1 Articles : 5 Articles
Three novel peptide sequences identified from palm kernel cake (PKC) generated protein\nhydrolysate including YLLLK,WAFS and GVQEGAGHYALL were used for stability study against\nangiotensin-converting enzyme (ACE), ACE-inhibition kinetics and molecular docking studies.\nResults showed that the peptides were degraded at different cleavage degrees of 94%, 67% and\n97% for YLLLK, WAFS and GVQEGAGHYALL, respectively, after 3 h of incubation with ACE.\nYLLLK was found to be the least stable (decreased ACE-inhibitory activity) compared to WAFS and\nGVQEGAGHYALL (increased ACE-inhibitory activity). YLLLK showed the lowest Ki (1.51 mM) in\ninhibition kinetics study when compared to WAFS and GVQEGAGHYALL with Ki of 2 mM and\n3.18 mM, respectively. In addition, ACE revealed the lowest Kapp\nm and Vapp\nmax and higher catalytic\nefficiency (CE) in the presence of YLLLK at different concentrations, implying that the enzyme\ncatalysis decreased and hence the inhibition mode increased. Furthermore, YLLLK showed the lowest\ndocking score of -8.224 and seven interactions with tACE, while peptide GVQEGAGHYALL showed\nthe higher docking score of -7.006 and five interactions with tACE....
The programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) is\nan immune checkpoint (ICP) overexpressed in various types of tumors; thus, it has been considered\nas an important target for cancer therapy. To determine important residues for ligand binding,\nwe applied molecular docking studies to PD-1/PD-L1 complex inhibitors against the PD-L1 protein.\nOur data revealed that the residues Tyr56, Asp122, and Lys124 play critical roles in ligand binding to\nthe PD-L1 protein and they could be used to design ligands that are active against the PD-1/PD-L1\ncomplex. The formation of H-bonds with Arg125 of the PD-L1 protein may enhance the potency of\nthe PD-1/PD-L1 binding....
The blockade of the programmed cell death protein 1/programmed cell death ligand\n1 (PD-1/PD-L1) pathway plays a critical role in cancer immunotherapy by reducing the immune\nescape. Five monoclonal antibodies that antagonized PD-1/PD-L1 interaction have been approved by\nthe Food and Drug Administration (FDA) and marketed as immunotherapy for cancer treatment.\nHowever, some weaknesses of antibodies, such as high cost, low stability, poor amenability for oral\nadministration, and immunogenicity, should not be overlooked. To overcome these disadvantages,\nsmall-molecule inhibitors targeting PD-L1 were developed. In the present work, we applied in\nsilico and in vitro approaches to develop short peptides targeting PD-1 as chemical probes for the\ninhibition of PD-1â??PD-L1 interaction. We first predicted the potential binding pocket on PD-1/PD-L1\nproteinâ??protein interface (PPI). Sequentially, we carried out virtual screening against our in-house\npeptide library to identify potential ligands. WANG-003,WANG-004, andWANG-005, three of our\nin-house peptides, were predicted to bind to PD-1 with promising docking scores. Next, we conducted\nmolecular docking and molecular dynamics (MD) simulation for the further analysis of interactions\nbetween our peptides and PD-1. Finally, we evaluated the affinity between peptides and PD-1 by\nsurface plasmon resonance (SPR) binding technology. The present study provides a new perspective\nfor the development of PD-1 inhibitors that disrupt PD-1â??PD-L1 interactions. These promising\npeptides have the potential to be utilized as a novel chemical probe for further studies, as well as\nproviding a foundation for further designs of potent small-molecule inhibitors targeting PD-1....
The effect of analogue Pd(II)-, Pt(II)-, and Au(III) compounds featuring\n2-(2â??-pyridyl)benzimidazole on the aggregation propensity of amyloid-like peptides derived from\nABeta and from the C-terminal domain of nucleophosmin 1 was investigated. Kinetic profiles of\naggregation were evaluated using thioflavin binding assays, whereas the interactions of the\ncompounds with the peptides were studied by UV-Vis absorption spectroscopy and electrospray\nionization mass spectrometry. The results indicate that the compounds modulate the aggregation\nof the investigated peptides using different mechanisms, suggesting that the reactivity of the metal\ncenter and the physicochemical properties of the metals (rather than those of the ligands and the\ngeometry of the metal compounds) play a crucial role in determining the anti-aggregation\nproperties....
Pyridoxine/pyridoxal kinase (PdxK), belongs to the ribokinase family and is involved in\nthe vitamin B6 salvage pathway by phosphorylating 5-pyridoxal (PL) into an active form. In the\nhuman malaria parasite, Plasmodium falciparum, PfPdxK functions to salvage vitamin B6 from both\nitself and its host. Here, we report the crystal structure of PfPdxK from P. falciparum in complex\nwith a non-hydrolyzable ATP analog (AMP-PNP) and PL. As expected, the fold is retained and both\nAMP-PNP and PL occupy the same binding sites when compared to the human ortholog. However,\nour model allows us to identify a FIxxIIxL motif at the C terminus of the disordered repeat motif\n(XNXH)m that is implicated in binding the WD40 domain and may provide temporal control of\nPfPdxK through an interaction with a E3 ligase complex. Furthermore, molecular docking approaches\nbased on our model allow us to explain differential PfPdxK phosphorylation and activation of a\nnovel class of potent antimalarials (PT3, PT5 and PHME), providing a basis for further development\nof these compounds. Finally, the structure of PfPdxK provides a high-quality model for a better\nunderstanding of vitamin B6 synthesis and salvage in the parasite....
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