Computational screening of branched cyclic peptide motifs as potential enzyme mimetics

2003 ◽  
Vol 9 (3) ◽  
pp. 145-155 ◽  
Author(s):  
Athanassios Stavrakoudis ◽  
Sevasti Makropoulou ◽  
Vassilios Tsikaris ◽  
Maria Sakarellos-Daitsiotis ◽  
Constantinos Sakarellos ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Motifs ◽  
Computational Screening ◽  
Enzyme Mimetics

scholarly journals Luminescent Iridium Complex-Peptide Hybrids (IPHs) for Therapeutics of Cancer: Design and Synthesis of IPHs for Detection of Cancer Cells and Induction of Their Necrosis-Type Cell Death

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Abdullah-Al Masum ◽  
Yosuke Hisamatsu ◽  
Kenta Yokoi ◽  
Shin Aoki
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Cyclic Peptide ◽  
Death Receptors ◽  
Iridium Complex ◽  
Peptide Motifs ◽  
Design And Synthesis ◽  
Cancer Cell Death ◽  
Promising Tool

Death receptors (DR4 and DR5) offer attractive targets for cancer treatment because cancer cell death can be induced by apoptotic signal upon binding of death ligands such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with death receptors. Cyclometalated iridium(III) complexes such asfac-Ir(tpy)3(tpy = 2-(4-tolyl)pyridine) possess aC3-symmetric structure like TRAIL and exhibit excellent luminescence properties. Therefore, cyclometalated Ir complexes functionalized with DR-binding peptide motifs would be potent TRAIL mimics to detect cancer cells and induce their cell death. In this study, we report on the design and synthesis ofC3-symmetric and luminescent Ir complex-peptide hybrids (IPHs), which possess cyclic peptide that had been reported to bind DR5. The results of 27 MHz quartz-crystal microbalance (QCM) measurements of DR5 with IPHs and costaining experiments of IPHs and anti-DR5 antibody, suggest that IPHs bind with DR5 and undergo internalization into cytoplasm, possibly via endocytosis. It was also found that IPHs induce slow cell death of these cancer cells in a parallel manner to the DR5 expression level. These results indicate that IPHs may offer a promising tool as artificial luminescent mimics of death ligands to develop a new category of anticancer agents that detect and kill cancer cells.

scholarly journals Transmembrane Self-Assembled Cyclic Peptide Nanotubes Based on α‐Residues and Cyclic δ‐Amino Acids: A Computational Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Alexandre Blanco-González ◽  
Martín Calvelo ◽  
Pablo F. Garrido ◽  
Manuel Amorín ◽  
Juan R. Granja ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Computational Study ◽  
Peptide Nanotubes ◽  
Peptide Motifs ◽  
Self Assembling ◽  
Transmembrane Channels ◽  
Dynamics Simulations ◽  
Cyclic Peptide Nanotubes

Self-assembling cyclic peptide nanotubes have been shown to function as synthetic, integral transmembrane channels. The combination of natural and nonnatural aminoacids in the sequence of cyclic peptides enables the control not only of their outer surface but also of the inner cavity behavior and properties, affecting, for instance, their permeability to different molecules including water and ions. Here, a thorough computational study on a new class of self-assembling peptide motifs, in which δ-aminocycloalkanecarboxylic acids are alternated with natural α-amino acids, is presented. The presence of synthetic δ-residues creates hydrophobic regions in these α,δ-SCPNs, which makes them especially attractive for their potential implementation in the design of new drug or diagnostic agent carrier systems. Using molecular dynamics simulations, the behavior of water molecules, different ions (Li+, Na+, K+, Cs+, and Ca2+), and their correspondent counter Cl− anions is extensively investigated in the nanoconfined environment. The structure and dynamics are mutually combined in a diving immersion inside these transmembrane channels to discover a fascinating submarine nanoworld where star-shaped water channels guide the passage of cations and anions therethrough.

Biologically Active Cyclic Peptide from Collectotrichum sp.

Planta Medica ◽  
2008 ◽  
Vol 74 (03) ◽  
Author(s):  
HMTB Herath ◽  
SI Khan ◽  
B Tekwani ◽  
NPD Nanayakkara
Keyword(s):  
Cyclic Peptide ◽  
Biologically Active

A Target-Based Method for Designing Heterochiral Cyclic Peptide Binders: De Novo Inhibitors of the PD-1/PD-L1 Interaction

2020 ◽  
Author(s):  
Salvador Guardiola ◽  
Monica Varese ◽  
Xavier Roig ◽  
Jesús Garcia ◽  
Ernest Giralt
Keyword(s):  
Protein Interactions ◽  
Cyclic Peptides ◽  
General Framework ◽  
Large Scale ◽  
Cyclic Peptide ◽  
De Novo ◽  
Inhibitory Effect ◽  
Original Text ◽  
Retraction Notice ◽  
Pharmaceutical Properties

<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>

Tuning the Redox Activity of Metal−Organic Frameworks for Enhanced, Selective O2 Binding

2019 ◽  
Author(s):  
Andrew Rosen ◽  
M. Rasel Mian ◽  
Timur Islamoglu ◽  
Haoyuan Chen ◽  
Omar Farha ◽  
...  
Keyword(s):  
Density Functional ◽  
Metal Organic Frameworks ◽  
Redox Activity ◽  
Screening Methods ◽  
Bridging Ligands ◽  
Metal Centers ◽  
Computational Screening ◽  
Open Metal Sites ◽  
Metal Organic ◽  
Unsaturated Metal Sites

<p>Metal−organic frameworks (MOFs) with coordinatively unsaturated metal sites are appealing as adsorbent materials due to their tunable functionality and ability to selectively bind small molecules. Through the use of computational screening methods based on periodic density functional theory, we investigate O<sub>2</sub> and N<sub>2</sub> adsorption at the coordinatively unsaturated metal sites of several MOF families. A variety of design handles are identified that can be used to modify the redox activity of the metal centers, including changing the functionalization of the linkers (replacing oxido donors with sulfido donors), anion exchange of bridging ligands (considering μ-Br<sup>-</sup>, μ-Cl<sup>-</sup>, μ-F<sup>-</sup>, μ-SH<sup>-</sup>, or μ-OH<sup>-</sup> groups), and altering the formal oxidation state of the metal. As a result, we show that it is possible to tune the O<sub>2</sub> affinity at the open metal sites of MOFs for applications involving the strong and/or selective binding of O<sub>2</sub>. In contrast with O<sub>2</sub> adsorption, N<sub>2</sub> adsorption at open metal sites is predicted to be relatively weak across the MOF dataset, with the exception of MOFs containing synthetically elusive V<sup>2+</sup> open metal sites. As one example from the screening study, we predict that exchanging the μ-Cl<sup>-</sup> ligands of M<sub>2</sub>Cl<sub>2</sub>(BBTA) (H<sub>2</sub>BBTA = 1<i>H</i>,5<i>H</i>-benzo(1,2-d:4,5-d′)bistriazole) with μ-OH<sup>-</sup> groups would significantly enhance the strength of O<sub>2</sub> adsorption at the open metal sites without a corresponding increase in the N<sub>2</sub> affinity. Experimental investigation of Co<sub>2</sub>Cl<sub>2</sub>(BBTA) and Co<sub>2</sub>(OH)<sub>2</sub>(BBTA) confirms that the former exhibits only weak physisorption, whereas the latter is capable of chemisorbing O<sub>2</sub> at room temperature. The chemisorption behavior is attributed to the greater electron-donating character of the μ-OH<sup>-</sup><sub> </sub>ligands and the presence of H-bonding interactions between the μ-OH<sup>-</sup> bridging ligands and the O<sub>2</sub> adsorbate.</p>

Efficient Prediction of Structural and Electronic Properties of Hybrid 2D Materials Using DFT and Machine Learning

2018 ◽  
Author(s):  
Sherif Tawfik ◽  
Olexandr Isayev ◽  
Catherine Stampfl ◽  
Joseph Shapter ◽  
David Winkler ◽  
...  
Keyword(s):  
Machine Learning ◽  
Band Gap ◽  
Density Functional ◽  
2D Materials ◽  
Van Der Waals ◽  
Building Blocks ◽  
Machine Learning Techniques ◽  
Interlayer Distance ◽  
Computational Screening ◽  
Wide Range

Materials constructed from different van der Waals two-dimensional (2D) heterostructures offer a wide range of benefits, but these systems have been little studied because of their experimental and computational complextiy, and because of the very large number of possible combinations of 2D building blocks. The simulation of the interface between two different 2D materials is computationally challenging due to the lattice mismatch problem, which sometimes necessitates the creation of very large simulation cells for performing density-functional theory (DFT) calculations. Here we use a combination of DFT, linear regression and machine learning techniques in order to rapidly determine the interlayer distance between two different 2D heterostructures that are stacked in a bilayer heterostructure, as well as the band gap of the bilayer. Our work provides an excellent proof of concept by quickly and accurately predicting a structural property (the interlayer distance) and an electronic property (the band gap) for a large number of hybrid 2D materials. This work paves the way for rapid computational screening of the vast parameter space of van der Waals heterostructures to identify new hybrid materials with useful and interesting properties.

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