MiniFrag Library

Conventional fragment-based drug discovery (FBDD) using X-ray crystallographic screening applies protein crystal soaking with a moderate ligand concentration (50-100 mM) to identify fragments that bind to the target. These fragments are then evolved into drug-like molecules through an iterative cycle of medicinal chemistry and the structural determination of protein-ligand complexes. The characteristic of fragment binding is that the energy at the ligand binding hotspot on the protein surface is optimal leading to highly ligand-efficient. In addition, fragment soaking interrogates the surface of the protein in a site-agnostic manner, thus it can detect binding in an unprecedented pocket with potential applications for drug discovery. A major benefit of fragment screening is the high efficiency of chemical space sampling. The molecular complexity and the size of the molecular space increases with heavy atom count (HAC), and the chance of observing good complementarity with the protein decreases with the chemical complexity of the ligand. Combining modern and sophisticated crystallographic methods with the intelligent design of chemical libraries can make breakthroughs in our understanding of protein structure changes and behaviors. X-ray crystallography can detect hits with ultra-low affinity well but requires exposure of crystal to increasing concentrations of compound to reliably identify these binding events.

BOC Sciences proposes a crystal-soaking method that uses a high concentration (1 M) aqueous solution soaks of a a dedicated library of ultra-low molecular weight compounds. Our well-designed MiniFrag library is specially constructed for sampling the chemical space in the ultra-low molecular weight range.

Advantages of Our Methodology

• It retains the high sensitivity required to strictly interrogate a protein’s molecular recognition maps
• It can provide hit substances that deliver information for the development of chemical biology tools and guide structure-based design

Figure 1. Pictorial summary of the crystallographic screening method. (Nienaber, V. L.; et al. 2000)

MiniFrag Library Characteristics

At BOC Sciences, our Minifrag library consists of more than 80 chemically diverse and highly soluble ligands containing 5 to 7 non-hydrogen atoms 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 MiniFrag Library characteristics

Features of MiniFrag Library

• We create a MiniFrag Library for FBDD, mainly guided by the well-known Rule of Three
• Multiple filtering criteria (physical and chemical filters) are applied to BOC Sciences General Fragment Library to generate our MiniFrag Library
• Allows for identification of hot and warm spots on proteins
• Specifically constructed to sample chemical space in the ultra-low-molecular-weight regime and comprises hundreds of chemically diverse and highly soluble fragments
• The undesirable function is eliminated by applying PAINS and our unique in-house medicinal chemical filters
• Theses mini fragments are screened at approximately 1 M to observe binding as they are very small
• In order to facilitate the soaking of these compounds at such high concentrations, they are all chosen to be soluble in water without the need for organic solvents such as DMSO
• In our library, these compounds are provided at a concentration of 2 M to be soaked at a concentration of 1 M in the chosen crystallization conditions
• Our MiniFrag library is offered in a variety of different formats to allow flexibility in its use
• The library can be both used for fragment soaking or co-crystallization which is depend on which method is best for the project
• Cherry-picking is available

What We Deliver

• Delivered within 2 weeks in any customer-preferred format
• All compounds have a minimum purity of 90% assessed by ¹H NMR
• Screening at 1M suggests that the fragments would be provided dry, ready for dissolution prior to protein soaking
• Analytical data is provided

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