Cysteine focused Covalent Fragments

Cysteine is the most common covalent amino acid residue. Its side chain has an electron-rich active sulfhydryl (SH) group which can be used as a nucleophile to attack the electrophilic group in drug molecules in biochemical reactions. The SH group can form a disulfide bond (SS) through covalent linkage with another cysteine residue, which will lead to a covalent bond through a certain conformational change or transition state eventually. Most inhibitors work by covalently bonding with cysteine residues. Nowadays, covalent chemical probes have become important tools for drug discovery. The number of successful applications in the evaluation of protein pharmacological properties is impressive, especially focusing on Cys residues, which brings aspiration for the discovery and synthesis of new covalent modifiers.

BOC Sciences can construct a Cysteine focused Covalent Fragment Library based on specific structure moieties that could react reversibly or irreversibly with cysteine residues of a drug target.

Figure 1. Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors. (Gehringer, M.; Laufer, S. A. 2019)

Advanced Covalent Warhead

BOC Sciences employs the following covalent warheads to select covalent inhibitors focused on Cys residue from our HTS Compound Collection:

Cysteine focused Covalent Fragments Characteristics

At BOC Sciences, our Cysteine focused Covalent Fragment Library is consist of more than 3,000 fragment molecules, which is a reliable source of high-quality fragments. We cooperate with leading experts in the field of FBDD to design and supply top-level fragment libraries, aiming to meet different requirement of each client.

Table1. The summary of the BOC Sciences Cysteine focused Covalent Fragments characteristics

Features of Cysteine focused Covalent Fragments

• Deep knowledge-based method is applied to design and synthesize our Cysteine Focused Covalent Fragment Library
• Multiple filtering criteria (physical and chemical filters) are applied to BOC Sciences General Fragment Library to generate high quality Cysteine focused Covalent Fragments
• The undesirable function is eliminated using PAINS and our in-house developed reactivity filters
• The covalent warheads are carefully selected by our experienced chemists based on their reactivity and reflected a small set of specific structural filters
• The electrophilic fragments selected by the structural filter are then analyzed to remove any molecules with trivial or unwanted structural features
• Only well-proven covalent warheads can form adducts that are easy to interpret
• Our well-designed Cysteine Focused Fragment Library contains fragments with described reactivity
• Attractive scaffolding is able to be derived from the latest core building blocks
• All compounds with side functional groups that interfere under most of the reaction conditions have been successfully removed from our library
• Cherry-picking is available

What We Deliver

• Delivered within 2 weeks and is available for prompt delivery in various formats
• Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
• All compounds have a minimum purity of 90% assessed by ¹H NMR
• Spectral data is available

BOC Sciences provides professional, rapid and high-quality services of Cysteine focused Covalent Fragments design at competitive prices for global customers. Personalized and customized services of Cysteine focused Covalent Fragments design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!