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Halogen-Enriched Fragments

Halogen-Enriched Fragment LibraryOur Halogen-Enriched Fragment Library comprises 618 brominated fragments that can explore binding sites for favorable halogen bond interactions to identify unique binding modes that are complementary to those obtained from classical fragment-based screening.
 

The library is intended for more effective identification of the fragment bound in the active site of a drug target by X-ray crystallography.

 

Halogen bonds have recently attracted increased interest in molecular design offering alternatives to classical polar interactions such as hydrogen bonds. Halogen bonds involving main-chain carbonyl oxygens were found to improve the binding of several ligands to their target protein significantly. The most frequently observed halogen bonds in protein−ligand structures are either halogen−carbonyl oxygen or halogen−π interactions. Quantum chemical calculations also suggest that affinity and selectivity of ligands can be increased by directed halogen−sulfur contacts with methionines. Despite this potential of halogen moieties to contribute favorably to ligand binding, the number of compounds containing heavy halides in standard libraries for fragment-based screening is very low.

 

Halogen-Enriched Fragment Library designed by OTAVAchemicals uses criteria for fragment selection similar to the “rule of three”. As an additional cheminformatics selection rule, the molecules were required to contain at least one bromine atom.


The following compounds were REMOVED from the library:

  • compounds containing any atom different to O, N, C, H, Br, I, Cl, F, S, or P
  • compounds that do not contain at least one aliphatic or aromatic ring.
  • compounds containing more than 4 halogen atoms
  • compounds containing reactive functional groups bearing the risk of covalent binding to the target protein
  • compounds containing functionalities that can cause undesirable effects such as: Cancerogenic, Toxicity, ADME problems, False positives
All compounds are in stock (20mg min. amount), cherry-picking is available.


The summary of the OTAVAchemicals Halogen-Enriched Fragment Library characteristics:
 
 
Parameter Value Average
MW  < 300 246.8
CLogP < 3 2.1
Number of Rotatable Bonds ≤ 3 1.3
Number of H Donors ≤ 3 0.9
Number of H Acceptors ≤ 4 2.2
PSA < 80 44.2
Number of Rings > 0 1.6
LogSw > -5 -3.0
Sum of Halogen Atoms ≤ 4  
Compounds with "undesirable" functionalities Removed  
Compound amount in stock > 20mg  


On your request our experts will choose functionalities as appropriate groups to allow rapid chemistry to be applied to the fragments for evolution of the compounds. Custom parameter filtering is also possible.

 

 

The library (SDF, XLS, PDF format) is available on request. Feel free to contact us or use on-line form below to send an inquiry if you are interested to obtain this library or if you need more information.

 

 

 



Wilcken R, Liu X, Zimmermann MO, Rutherford TJ, Fersht AR, Joerger AC, Boeckler FM. Halogen-enriched fragment libraries as leads for drug rescue of mutant p53. J Am Chem Soc. 2012, 134(15):6810-8.

 

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