Posts Tagged “drug discovery”

The Advances and Future Development of Structural Mass Spectrometry in Biologicals

Mass spectrometry (MS) is one of the key techniques for protein characterization/ protein detection. In this article, I will present some techniques, including electron transfer dissociation mass spectrometry (ETDMS). MS applications are also described as well as the stability evaluation of alternatives molecular biological products in the future.

Since about 30 years ago, the introduction of recombinant human insulin as a treatment drug, biologics (therapeutic proteins) has become the second largest product type after the biopharmaceutical vaccines. Compared with small molecule drugs, biologics have several different advantages, including high specificity, high efficiency, long circulating half-life, fewer side effects and a higher regulation approval rate. These drugs have been used therapeutically in the treatment of many life-threatening diseases, such as cancer, infectious diseases, genetic diseases, and inflammation. Currently, pharmaceutical companies are more committed to biological products. According to statistics, in 2011, the biological products market has reached approximately $102.4 million, with an increase rate of 9.6% compared to that of 2010. In biological products (drug discovery), there are two types of protein: target proteins (found in the body) and therapeutic proteins (drug alternatives). Target protein normally exists as a set of molecules, and therapeutic protein specifically binds to a selected target protein in vivo or in vitro. In drug discovery, the goal is to find a drug alternative that has excellent biophysical, pharmacokinetics (PK) and pharmacodynamic (PD) properties to maximize opportunities for success through downstream development. Because from the earliest stages of drug discovery to marketing stage, it can take15 years to develop a new therapeutic protein.

MS application in structural studies of biological products

In most cases, biological products produced by recombinant DNA technology is complex, heterogeneous, and subject to various modifications affection, while the biological efficacy of biological products, clearance, safety and immunogenicity is highly dependent on its structure. Therefore, demand in structural characterization of proteins is growing, especially in the drug discovery phase when a large number of alternatives are still there.

Molecular weight and amino acid sequence

The first step to describe therapeutic protein characteristics is to measure MW and confirm its AA sequence. It is critical to determine the product identity and integrity.

Post-translational modifications [PTM]: glycosylation, chemical modification, and S-S connection

All approved biological products currently in development or have post-translational modifications (PTMs) may deeply affect therapeutic applications of associated proteins.