We utilize the latest technologies to design proteins and peptide drugs that target chemokines.
Our main focus is to identify chemokines and their associated receptors to develop novel synthetic peptides to treat diseases by exploiting the natural chemokine system.
Our approach consists of a combination of the following elements:
A great deal of information is known about chemokines including their roles, linear amino acid sequence, 3-dimensional structure, genetic sequence, molecular weight and binding sites. We leverage this information to identify the binding sites on chemokines which bind to receptors on the surface of various cells in the body. We select chemokines and those important binding sites for further study and potentially to manufacture them synthetically. These synthetic peptides are called analogs. We produce analogs that have the potential to replace proteins for those chemokines that cannot be produced naturally due to either their breakdown, instability or their aggregation in the body. We synthetically produce chemokines that are believed to have important therapeutic properties and potentially represent large markets.
Our understanding of the 3-dimensional structure and binding of a chemokine with its receptor is essential for the design of a smaller chemokine analog of its natural counterpart.
Redesign of the original drug candidate is required as part of the rational peptide design process. The changing of one linkage or an amino acid can cause the drug candidate to enhance or counteract the biological activities of their natural counterparts, or improve the pharmacokinetics. We continually redesign in an effort to obtain more desirable peptides.
We use solid phase peptide synthesis to generate several amino acid peptides of relatively short length, typically 5 to 15 amino acids, or large sequence peptides, typically 15 - 70 amino acids in length. The technology allows the cost effective production of peptides with yield levels that are greater than observed with recombinant protein production. This is achieved synthetically through organic chemistry. This process also allows for the introduction of non-natural amino acids and other chemical groups into peptides, allowing for rational design of a drug candidate.
Systematic screening of promising chemokines is performed through receptor binding studies. Analogs bearing the desired biological and chemical properties of a desired therapeutic are candidates for animal model evaluation.
Novel drug candidates are evaluated in animal models of the disease to assess safety and efficacy. The first animal models are typically mice or rats. These studies are categorized as preclinical studies.
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