The modern drug discovery process, in general, involves the identification of a biochemical target (usually protein target), screening of synthetic compounds or compound libraries from combinatorial chemistry/natural sources for a lead compound, and optimization of the lead compound (activity, selectivity, pharmacokinetics, etc.) for recommending a potential clinical candidate. | 19 LC MS ANALYSIS OF PROTEINS AND PEPTIDES IN DRUG DISCOVERY Guodong Chen Yan-Hui Liu and Birendra N. Pramanik INTRODUCTION The modern drug discovery process in general involves the identification of a biochemical target usually protein target screening of synthetic compounds or compound libraries from combinatorial chemistry natural sources for a lead compound and optimization of the lead compound activity selectivity pharmacokinetics etc. for recommending a potential clinical candidate. The ultimate goal is to develop highly potent compounds small molecules that bind noncovalently with target proteins and produce the desired therapeutic response with minimal side effects 1 . In addition the discovery of DNA structures by Francis Crick and James Watson laid a foundation for the 30 billion-a-year biotechnology industry that has produced some 160 drugs and vaccines treating everything from breast cancer to diabetes. Recent advances in recombinant DNA technology have provided means to produce and develop protein products as novel drugs vaccines and diagnostic agents. For example INTRON A interferon a-2b is one of the first recombinant protein drugs introduced on the market. This synthetic E. coli recombinant DNA-derived protein functions as a natural interferon produced by the human body as part of the immune system in response to the presence of enemy cells. It not only interferes with foreign invaders that may cause infections but also prevents the growth and spread of other diseased HPLC for Pharmaceutical Scientists Edited by Yuri Kazakevich and Rosario LoBrutto Copyright 2007 by John Wiley Sons Inc. 837 838 LC MS ANALYSIS OF PROTEINS AND PEPTIDES IN DRUG DISCOVERY cells in the body. This protein drug is effective in treating hepatitis C virus and a variety of tumors. ENBREL etanercept is another protein drug used for treatment of rheumatoid arthritis. It is produced from a Chinese hamster ovary mammalian cell expression system. This protein drug is a .
