LATEST NEWS

02.02.2012

San Diego: CalAsia Pharmaceuticals and Professor R. Padmanabhan of Georgetown University announce a collaboration to develop inhibitors of Dengue and West Nile virus protoeases.

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TECHNOLOGY

Crystallography

CalAsia Pharmaceuticals core technology is to use the three dimensional structural information of the hits, early leads and drug molecules bound to its targets to discover and develop clinical candidates in an expeditious manner. CalAsia scientists have been the lead crystallographer and core members of the team that discovered Nesina, a drug to treat Type 2 Diabetes and MK-4965, a clinical candidate, for the treatment of HIV-1 AIDS using structure based methods. The team has successfully solved three-dimensional crystal structures of number of proteins involved in Parkinson's Disease, Oncology, Type 2 Diabetes, Cardiovascular Disease, Obesity and Infectious Disease representing kinases, proteases, molecular chaperones, membrane associated proteins, phosphatases, fatty acid binding proteins, reverse transcriptase, phosphodiestrases, nucleotide binding proteins, acetyl coA carboxylase and many more. Our crystallography strengths included but are not limited to:

Design and clone gene constructs of drug targets suitable to yield recombinant proteins in sufficient quantity and purity that will result in diffraction quality crystals suitable for fragment screening and structure based lead optimization.

Optimization of the expression conditions in E. coli and yeast systems to obtain soluble, biologically active proteins for crystallization experiments.

Parallel crystallization screening experiments of multiple variants of drug targets to increase the success rate of obtaining crystals.

Optimization of initial crystal hits using various techniques including macro-, micro-, streak and cross-seeding.

Extensive knowledge of successfully producing crystals of the compounds and drug candidates bound to the drug targets:

  1. Soaking experiments
  2. Pre-complexation followed by crystallization screening
  3. Soak in soak out technique

Access to multiple synchrotron beam lines for rapid and superior quality x-ray intensity data.

    Proven expertise in solving three-dimensional structure of drug targets by:

  1. Molecular replacement
  2. Heavy atom ab initio phasing
  3. Single anomalous dispersion phasing method (SAD)
  4. Multiple anomalous dispersion phasing method (MAD)
  5. Combination of partial model and experimental phasing
  6. Non-crystallography symmetry averaging