Systematic optimization of large macrocyclic peptide ligands is a serious challenge. Here, we describe an approach for lead-optimization using the PD-1/PD-L1 system as a retrospective example of moving from initial lead compound to clinical candidate. We show how conformational restraints can be derived by exploiting NMR data to identify low-energy solution ensembles of a lead compound. Such restraints can be used to focus conformational search for analogs in order to accurately predict bound...
[ASAP] NMR Relaxation Dispersion Reveals Macrocycle Breathing Dynamics in a Cyclodextrin-based Rotaxane
NMR Relaxation Dispersion Reveals Macrocycle Breathing Dynamics in a Cyclodextrin-based Rotaxane
Shannon Stoffel†, Qi-Wei Zhang§, Dong-Hao Li†, Bradley D. Smith†, and Jeffrey W. Peng*†?
https://pubs.acs.org/na101/home/literatum/publisher/achs/journals/content/jacsat/0/jacsat.ahead-of-print/jacs.9b12524/20200408/images/medium/ja9b12524_0007.gif
Journal of the American Chemical Society
DOI: 10.1021/jacs.9b12524
http://feeds.feedburner.com/~r/acs/jacsat/~4/oHHm-vBMmPQ
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[NMR paper] Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
Related Articles Thiourea-Based Inhibitors of the B-Cell Lymphoma 6 (BCL6) BTB Domain via NMR-Based Fragment Screening and Computer-Aided Drug Design.
J Med Chem. 2018 Jul 03;:
Authors: Cheng H, Linhares B, Yu W, Cardenas MG, Ai Y, Jiang W, Winkler A, Cohen S, Melnick A, MacKerell AD, Cierpicki T, Xue F
Abstract
Protein-protein interactions (PPI) between the transcriptional repressor B-cell...
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Postdoc position at Utrecht University: solid-state NMR-based design of membrane-active peptide-antibiotics
From The DNP-NMR Blog:
Postdoc position at Utrecht University: solid-state NMR-based design of membrane-active peptide-antibiotics
A 2.5 years postdoc position in the structural characterisation and design of novel peptide-antibiotics is available in the Weingarth group at Utrecht University, the Netherlands.
The project is set within the context of the rapid development of antimicrobial resistance that urgently calls for novel antibiotics with unexploited mechanisms.
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04-18-2018 01:41 PM
[NMR paper] A Ligand-Based NMR Screening Approach for the Identification and Characterization of Inhibitors and Promoters of Amyloid Peptide Aggregation.
A Ligand-Based NMR Screening Approach for the Identification and Characterization of Inhibitors and Promoters of Amyloid Peptide Aggregation.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7315-19-Wiley_FullText_120x30_orange.png Related Articles A Ligand-Based NMR Screening Approach for the Identification and Characterization of Inhibitors and Promoters of Amyloid Peptide Aggregation.
ChemMedChem. 2017 Sep 07;12(17):1458-1463
Authors: Dalvit C, Santi S, Neier R
Abstract
Over the...
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[NMR paper] NMR Structure-Based Optimization of Staphylococcus aureus Sortase A Pyridazinone Inhibitors.
NMR Structure-Based Optimization of Staphylococcus aureus Sortase A Pyridazinone Inhibitors.
Related Articles NMR Structure-Based Optimization of Staphylococcus aureus Sortase A Pyridazinone Inhibitors.
Chem Biol Drug Des. 2017 Feb 03;:
Authors: Chan AH, Yi SW, Weiner EM, Amer BR, Sue CK, Wereszczynski J, Dillen CA, Senese S, Torres JZ, Andrew McCammon J, Miller LS, Jung ME, Clubb RT
Abstract
Staphylococcus aureus is a leading cause of hospital-acquired infections in the United States and is a major health concern as...
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[NMR paper] NMR Screening in Fragment-Based Drug Design: A Practical Guide.
NMR Screening in Fragment-Based Drug Design: A Practical Guide.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles NMR Screening in Fragment-Based Drug Design: A Practical Guide.
Methods Mol Biol. 2015;1263:197-208
Authors: Kim HY, Wyss DF
Abstract
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01-28-2015 03:22 AM
[NMR paper] Structure-based drug design: NMR-based approach for ligand-protein interactions.
Structure-based drug design: NMR-based approach for ligand-protein interactions.
Related Articles Structure-based drug design: NMR-based approach for ligand-protein interactions.
Drug Discov Today Technol. 2006;3(3):241-5
Authors: Zhang X, Tang H, Ye C, Liu M
Abstract
The realization of the powerfulness in analyzing ligand-protein interactions at the atomic resolution has made NMR techniques increasingly attractive in drug discovery and development. With some significant new method developments during the past few years,...
Complex peptide macrocycle optimization: combining NMR restraints with conformational analysis to guide structure-based and ligand-based design
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