Design, selection, and development of cyclic peptide ligands for human erythropoietin

2017 ◽  
Vol 1500 ◽  
pp. 105-120 ◽  
Author(s):  
William S. Kish ◽  
Hiroyuki Sachi ◽  
Amith D. Naik ◽  
Matthew K. Roach ◽  
Benjamin G. Bobay ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Ligands ◽  
Human Erythropoietin ◽  
Design Selection

Purification of human erythropoietin by affinity chromatography using cyclic peptide ligands

2018 ◽  
Vol 1085 ◽  
pp. 1-12 ◽  
Author(s):  
William S. Kish ◽  
Matthew K. Roach ◽  
Hiroyuki Sachi ◽  
Amith D. Naik ◽  
Stefano Menegatti ◽  
...  
Keyword(s):  
Affinity Chromatography ◽  
Cyclic Peptide ◽  
Peptide Ligands ◽  
Human Erythropoietin

scholarly journals Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1225
Author(s):  
Jiawen Cao ◽  
Tiantian Fan ◽  
Yanlian Li ◽  
Zhiyan Du ◽  
Lin Chen ◽  
...  
Keyword(s):  
Phage Display ◽  
Cyclic Peptide ◽  
Protein Complexes ◽  
Peptide Ligands ◽  
Phage Library ◽  
Cancer Drug ◽  
Protein Protein Interaction ◽  
Phage Display Technique ◽  
Peptide Mimic ◽  
Human Proteins

WD40 is a ubiquitous domain presented in at least 361 human proteins and acts as scaffold to form protein complexes. Among them, WDR5 protein is an important mediator in several protein complexes to exert its functions in histone modification and chromatin remodeling. Therefore, it was considered as a promising epigenetic target involving in anti-cancer drug development. In view of the protein–protein interaction nature of WDR5, we initialized a campaign to discover new peptide-mimic inhibitors of WDR5. In current study, we utilized the phage display technique and screened with a disulfide-based cyclic peptide phage library. Five rounds of biopanning were performed and isolated clones were sequenced. By analyzing the sequences, total five peptides were synthesized for binding assay. The four peptides are shown to have the moderate binding affinity. Finally, the detailed binding interactions were revealed by solving a WDR5-peptide cocrystal structure.

scholarly journals GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf

2020 ◽  
Vol 6 (10) ◽  
pp. 1753-1761 ◽  
Author(s):  
Ziyang Zhang ◽  
Rong Gao ◽  
Qi Hu ◽  
Hayden Peacock ◽  
D. Matthew Peacock ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Ligands

Design, Synthesis, and Evaluation of Linear and Cyclic Peptide Ligands for PDZ10 of the Multi-PDZ Domain Protein MUPP1†

Biochemistry ◽  
2007 ◽  
Vol 46 (44) ◽  
pp. 12709-12720 ◽  
Author(s):  
Sudhir C. Sharma ◽  
Chamila N. Rupasinghe ◽  
Rachel B. Parisien ◽  
Mark R. Spaller
Keyword(s):  
Cyclic Peptide ◽  
Pdz Domain ◽  
Peptide Ligands ◽  
Design Synthesis ◽  
Domain Protein

scholarly journals Discovery of Cyclic Peptide Ligands to the SARS-CoV-2 Spike Protein Using mRNA Display

2021 ◽  
Author(s):  
Alexander Norman ◽  
Charlotte Franck ◽  
Mary Christie ◽  
Paige M. E. Hawkins ◽  
Karishma Patel ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Peptide Ligands ◽  
Spike Protein ◽  
Mrna Display

Discovery of Cyclic Peptide Ligands to the SARS-CoV-2 Spike Protein using mRNA Display

2020 ◽  
Author(s):  
Alexander Norman ◽  
Charlotte Franck ◽  
Mary Christie ◽  
Paige M. E. Hawkins ◽  
Karishma Patel ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Dissociation Constants ◽  
Surface Protein ◽  
Peptide Ligands ◽  
Spike Protein ◽  
Mrna Display ◽  
Affinity Ligand ◽  
Protein Receptor ◽  
C Terminus ◽  
Diagnostic Applications

ABSTRACTThe COVID-19 pandemic, caused by SARS-CoV-2, has led to substantial morbidity, mortality and disruption globally. Cellular entry of SARS-CoV-2 is mediated by the viral spike protein and affinity ligands to this surface protein have the potential for applications as antivirals and diagnostic reagents. Here, we describe the affinity selection of cyclic peptide ligands to the SARS-CoV-2 spike protein receptor binding domain (RBD) from three distinct libraries (in excess of a trillion molecules each) by mRNA display. We identified six high affinity molecules with dissociation constants (KD) in the nanomolar range (15-550 nM) to the RBD. The highest affinity ligand could be used as an affinity reagent to detect spike protein in solution by ELISA, and the co-crystal structure of this molecule bound to the RBD demonstrated that it binds to a cryptic binding site, displacing a β-strand near the C-terminus. Our findings provide key mechanistic insight into the binding of peptide ligands to the SARS-CoV-2 spike RBD and the ligands discovered in this work may find future use as reagents for diagnostic applications.

scholarly journals Docking of peptides to GPCRs using a combination of CABS-dock with FlexPepDock refinement

2020 ◽  
Author(s):  
Aleksandra E Badaczewska-Dawid ◽  
Sebastian Kmiecik ◽  
Michał Koliński
Keyword(s):  
High Resolution ◽  
Molecular Mechanisms ◽  
Cyclic Peptide ◽  
Peptide Ligands ◽  
New Drugs ◽  
Structural Description ◽  
Deviation Measure ◽  
Peptide Complexes ◽  
High Resolution Models ◽  
G Protein Coupled

Abstract The structural description of peptide ligands bound to G protein-coupled receptors (GPCRs) is important for the discovery of new drugs and deeper understanding of the molecular mechanisms of life. Here we describe a three-stage protocol for the molecular docking of peptides to GPCRs using a set of different programs: (1) CABS-dock for docking fully flexible peptides; (2) PD2 method for the reconstruction of atomistic structures from C-alpha traces provided by CABS-dock and (3) Rosetta FlexPepDock for the refinement of protein–peptide complex structures and model scoring. We evaluated the proposed protocol on the set of seven different GPCR–peptide complexes (including one containing a cyclic peptide), for which crystallographic structures are available. We show that CABS-dock produces high resolution models in the sets of top-scored models. These sets of models, after reconstruction to all-atom representation, can be further improved by Rosetta high-resolution refinement and/or minimization, leading in most of the cases to sub-Angstrom accuracy in terms of interface root-mean-square-deviation measure.

DESIGNING DISULFIDE CYCLIC PEPTIDE AS FUSION INHIBITOR THAT TARGETS DENV ENVELOPE PROTEIN

2016 ◽  
Vol 78 (4-3) ◽  
Author(s):  
Usman Sumo Friend Tambunan ◽  
William Chua ◽  
Arli Aditya Parikesit ◽  
Djati Kerami
Keyword(s):  
Conformational Changes ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Peptide Ligands ◽  
Viral Envelope ◽  
Fusion Process ◽  
Dynamics Simulation ◽  
Health Concern ◽  
Fusion Inhibitor ◽  
Host Cell Membrane

Dengue has been a major health concern and currently there is no available option to treat the infection. It is an arboviral disease caused by dengue virus (DENV), an enveloped flavivirus. DENV initiates fusion process between viral envelope and host cell membrane, transfers its viral genome into target cell and infects host. Our research is focused on designing disulfide cyclic peptides that can fit into fusion cavity and interact with fusion peptide, interrupt conformational changes and therefore inhibit the fusion process. Computational approaches were conducted to calculate the binding affinity and stability of disulfide cyclic peptide ligands with target DENV E glycoprotein. Molecular docking and molecular dynamics simulation were performed using Molecular Operating Environment 2008.10 software (MOE 2008.10). Screening of 1320 designed ligands resulted in 3 best ligands, CLREC, CYREC and CYREC that can form interaction with target cavity and peptide fusion. These ligands showed good affinity with target DENV E glycoprotein based on free binding energy and interactions. To evaluate protein-ligand stability, we performed molecular dynamic simulation. Only CLREC showed protein-ligand stability and maintained interaction between ligand and target cavity. Therefore we propose CLREC as potential DENV fusion inhibitor candidates.  

scholarly journals Structural diversity in de novo cyclic peptide ligands from genetically encoded library technologies

2020 ◽  
Author(s):  
Tom E. McAllister ◽  
Oliver D. Coleman ◽  
Grace Roper ◽  
Akane Kawamura
Keyword(s):  
Cyclic Peptide ◽  
De Novo ◽  
Structural Diversity ◽  
Peptide Ligands
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