TECHNOLOGIES

NMX offers services that employ biophysical technologies and strategies to address clients' needs.

 

One of our main technologies is NMR spectroscopy.  This provides atomic-level information about compound solution properties and their interactions with target proteins.  

 

Rational strategies are key to revealing and evaluating compound properties and their interactions with proteins. NMX's library of strategies are extensive and based on some approaches we published in recent literature. Some examples of practical and quality-focused strategies are mentioned below.

 

Selected papers for:

 

Screening for ligand seeds for drug discovery.

 

 - Integrated Strategies for Identifying Leads that Target the NS3 Helicase of the Hepatitis C Virus, J. Med. Chem., (2014) DOI: 10.1021/jm401432c. Special HCV therapies issue. In press.

 - NMR Line-broadening and Transferred NOESY as a Medicinal Chemistry Tool for Studying Inhibitors of the Hepatitis C Virus NS3 Protease Domain, Bioorganic & Medicinal Chemistry Letters (2000), 10, 20, 2271-2274.

- Changes in Drug 13C NMR Chemical Shifts as a Tool for Monitoring Interactions With DNA, Biophysical Chemistry (2004), 109, 3, 333-344.

 

Triaging based on quality of ligand properties.  

 

- Integrated Strategies for Identifying Leads that Target the NS3 Helicase of the Hepatitis C Virus, J. Med. Chem., (2014) DOI: 10.1021/jm401432c. Special HCV therapies issue. 

- Monitoring Drug Self-Aggregation and Potential for Promiscuity in Off-Target In Vitro Pharmacology Screens by a Practical NMR Strategy, J. Med. Chem., (2013), 56, 17, 7073–7083.10.1021/jm401432c. Special HCV therapies issue. 

 

Structure- and dynamics-based drug discovery.

 

- Conformation-Based Restrictions and Scaffold Replacements in the Design of HCV Polymerase Inhibitors: Discovery of Deleobuvir (BI 207127), J. Med. Chem., (2014) DOI: 10.1021/jm4011862. Special HCV therapies issue. 

- Ligand Bioactive Conformation Plays a Critical Role in the Design of Drugs That Target the Hepatitis C Virus NS3 Protease, J. Med. Chem., (2014) DOI: 10.1021/jm401338c. Special HCV therapies issue. 

- Scaffold Hopping in the Rational Design of Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors, Bioorganic & Medicinal Chemistry Letters (2007), 17(12), 3362-3366.

- Importance of Ligand Bioactive Conformation in the Discovery of Potent Indole-Diamide Inhibitors of the Hepatitis C Virus NS5B, Journal of the American Chemical Society (2010), 132, 43, 15204-15212.

- Exploiting Ligand and Receptor Adaptability in Rational Drug Design Using Dynamics and Structure-based Strategies, Topics in Current Chemistry (2007), 272 (Bioactive Conformation I), 259-296.

 

Property-based drug design.

 

- Monitoring Drug Self-Aggregation and Potential for Promiscuity in Off-Target In Vitro Pharmacology Screens by a Practical NMR Strategy, J. Med. Chem., (2013), 56, 17, 7073–7083.

- Compound Aggregation in Drug Discovery: Implementing a Practical NMR Assay for Medicinal Chemists, J. Med. Chem., (2013), 56, 12, 5142–5150.

 

Primary structure determinations.

 

N- versus O-alkylation: Utilizing NMR Methods to Establish Reliable Primary Structure Determinations for Drug Discovery, Bioorganic & Medicinal Chemistry Letters, (2013), 23, 4663-4668.

 

Peptidomimetic drug design.  

 

Peptides as Leads for Drug Discovery, Eds Castanho, Miguel; Santos, Nuno C , Peptide Drug Discovery and Development (2011), 3-55.

 

Drug atropisomer chirality.  

 

- Enantiomeric Atropisomers Inhibit HCV Polymerase and/or HIV Matrix: Characterizing Hindered Bond Rotations and Target Selectivity, J. Med. Chem., (2014) DOI: 10.1021/jm401202a. Special HCV therapies issue. 

- Assessing Atropisomer Axial Chirality in Drug Discovery and Development, Journal of Medicinal Chemistry (2011), 54, 20, 7005-7022.

- Revealing Atropisomer Axial Chirality in Drug Discovery, ChemMedChem (2011), 6, 3, 505-513.