Covalent Fragment Library

In the early stages of drug discovery, compounds that can form covalent bonds with target proteins were filtered out by substructures, or are intentionally omitted as being too reactive, promiscuous, or toxic. However, covalent chemical probes have been widely used in drug discovery. Nowadays, covalent modifiers are used in treatment of arthritis and have been reported as antibacterial and antiviral agents. In addition, covalent modifiers also play a role in cancer treatment. The design of selective covalent irreversible inhibitors is very attractive but it is difficult to realize in practice. This is because it is challenging to achieve the right balance of molecular properties between reactivity and selectivity. At BOC Sciences, compounds of the Covalent Fragment Set are selected from our General Fragment Library based on the physical and chemical criteria of the fragments and the covalent binders that may exist in the molecule.

Advantages of Covalent Fragments

• Higher biochemical efficiency of target destruction
• Lower sensitivity toward pharmacokinetic parameters
• Increased duration of action
• Lifespan exceeds the pharmacokinetics of the compound

Figure 1. Covalent activator chemical structures and X-ray crystal structures of BtGH84_TM conjugates. (Darby, J. F.; et al. 2015)

Covalent Fragment Library Characteristics

BOC Sciences has synthesized over 18,000 novel covalent binders by parallel chemistry. The acquired knowledge on stability and selectivity has applied to the design of our Covalent Fragment Library. The library contains about 6,000 small molecule compounds for covalent fragment screening. 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 Covalent Fragment Library characteristics

Features of Covalent Fragment Library

• A wide range of chemical structure dissimilarity and are compliant with in-house PAINS structural filters
• All compounds are filtered according to the well-known Rule of Three
• A variety of physical and chemical parameters and medicinal chemical structure filters are applied to design our unique Covalent Fragment Library
• Choose warheads carefully: only experimentally confirmed reactivity, reported in the literature
• New modifications of well-known covalent part.
• Advanced covalent warhead: reactivity controlled covalent binders, N/O-sulfonyl fluoride, azididines, phosphonium, expoxides, 2-chloropropionamides.
• Fragments are plated by class and can be obtained separately
• A focused screening compound set is available for each of the indicated amino acid residue (cysteine, lysine, serine, histidine, threonine) according to customer requirements
• A set of preliminary covalent modifiers are created by selecting compounds with specific structural fragments (functional groups, warheads) that are known to form covalent bonds with amino acid residues in the binding site of the target protein, such as Lys, Cys, Ser, His and Tyr
• All compounds can be used for cherry-picking

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• 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
• Analytical data is provided

BOC Sciences provides professional, rapid and high-quality services of Covalent Fragment Library design at competitive prices for global customers. Personalized and customized services of Covalent Fragment Library 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!