Chemical Biology | SRI International

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Chemical Biology

SRI Biosciences’ Chemical Biology program tackles important problems in biology by translating fundamental research into new understanding and practical solutions.  The team implements expertise broadly across the biology/chemistry interface including: hit-to-lead, lead optimization, target discovery, synthetic method development, molecular probe design, assay development, structure-activity relationship/pharmacophore elucidation and process development.

Program Overview

Our team combines expertise in

  • Medicinal chemistry
  • Synthetic organic chemistry
  • Biochemistry
  • Compound screening
  • Protein structure/function

Our research programs fuel a rich pipeline of new drug-like molecules for applications in cancer, infection, immunology and neuro­degeneration, including diagnosis and treatment.

Research projects include:

  • Broad spectrum bactericidal agents for drug-resistant pathogens
  • Spliceosome modulators as antitumor lead compounds
  • Novel MAP4K4 (HGK) inhibitor for cancer therapy
  • Mechanism of action of Praziquantel (PZQ), a drug used for treatment of human schistosomiasis
  • Dual LOX inhibitors for prevention and treatment of Alzheimer’s disease
  • TGF-b agonists for the treatment of neurodegenerative diseases
  • Influenza RNA-dependent RNA polymerase (RdRp) inhibitors

Capabilities and Services

In addition to the Center’s research thrusts, our other capabilities include the following (click on a topic for additional detail):

Compound Screening

  • HTS, assay development, validation
  • Hit ID, characterization, validation
  • SAR modeling around screening hits
  • Phage display screening

Computational Chemistry

  • Virtual screening & clustering
  • Interpreting 2D, 3D, QSAR
  • In silico predictive ADMET

Hit to Lead Optimization

  • Design-focused libraries
  • Optimization for drug-like properties
  • Improve (DMPK) & toxicity
  • Select development candidate(s)

Custom Synthesis

  • Synthesis from mg to kg scale
  • Process development
  • Synthesis of reference standards
  • Radiolabeled synthesis

Peptides & Peptidomimetics

  • Design, synthesis & analysis
  • Pseudopeptides, peptoids & cyclic peptides
  • Lipidation, dye labeling & bioconjugation
  • Serum stability & prodrug design
  • Biophysical, structural, & chemical analyses

Protein Chemistry

  • Protein expression & purification mg to 100 mg scale
  • Informatics analysis of proteins & protein families
  • Determination of protein function using spectroscopic, structural, mutagenesis, & kinetics tools
  • Development of new protein-based/ enzymatic assays & bio-analytical methods

Fluorescence-Based in Vitro Diagnostics

  • Fluorogenic probes
  • Proteolytic enzyme profiling of biological samples
  • Substrate identification & optimization of recombinant enzymes

Proteomic Tools for Biomarker Discovery

  • Automated online 2D LC-MS/MS
  • Quantitative proteomics using isotopic labeling
  • Peptide sequencing & characterization
  • Selected & multiple reaction monitoring MS for biomarker validation
  • Identification & analysis of posttranslational modification
  • Bioinformatics for biomarker discovery