Halogen-Enriched Fragments Library

At present, halogen bonds have aroused increasing interest in molecular design in academia, which can provide an alternative to classical polar interactions (such as hydrogen bonds). Halogen bond is a non-covalent interaction of the type R-X···Y-R', where X is chlorine, bromine or iodine acting as a Lewis acid and Y can be any kind of Lewis base. Due to the insufficient electron density on the hind side of X along the R-X bond axis, chlorine, bromine and iodine have a characteristic region of positive electrostatic potential, that is, the σ-hole, which are beneficial to interact with electron donors. Scientists have found that the halogen bond involving the main-chain carbonyl oxygen significantly improves the binding of several ligands to their target proteins. Moreover, quantum chemistry calculations also show that the affinity and selectivity of ligands can be increased by directed halogen-sulfur contacts with methionine.

Figure 1. Halogen-Enriched Fragment Libraries as Leads for Drug Rescue of Mutant p53. (Wilcken, R.; et al. 2012)

Halogen-Enriched Fragments Library Design

• First, the fragment selection criteria of the 'Rule of Three' is employed to filter the General Fragment Library
• Second, an upper limit of the number of heavy atoms (up to 22) is used as an additional chemoinformatics selection rule, and the molecule needs to contain heavy halides, such as bromine, especially iodine
• Finally, small, non-reactive, soluble halogenated aromatic compounds are selected and tested using a thermal shift measurement (Differential Scanning Fluorescence, DSF), a secondary screening with ¹H/¹⁵N-HSQC NMR spectroscopy and isothermal titration calorimetry (ITC)

Halogen-Enriched Fragments Characteristics

At BOC Sciences, our Halogen-Enriched Fragments Library contains more than 700 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 Halogen-Enriched Fragment Library characteristics

Features of Halogen-Enriched Fragment Library

• We carefully remove the following compounds from the Halogen-Enriched Fragment Library:

Fragment molecules containing reactive functional groups that could bear the risk of covalent binding to the target protein

Compounds containing functionalities that can cause a series of undesirable effects

• We create a Halogen-Enriched Fragment Library for FBDD which complies with well-known Rule of Three
• Multiple filtering criteria (physical and chemical filters) are applied to BOC Sciences General Fragment Library to generate this unique library
• The undesirable function is eliminated by applying PAINS and our unique in-house medicinal chemical filters
• Cherry-picking is supported

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 Halogen-Enriched Fragment Library design at competitive prices for global customers. Personalized and customized services of Halogen-Enriched Fragments 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!