Antimicrobial peptides are gene-encoded peptide antibiotics. They are found in almost all living species and exhibit a broad spectrum of activity. Rather than interfere with a particular metabolic process, these peptides directly interact and permeablize microbial membranes. Up to now, resistance to antimicrobial peptides has been rarely observed. Consequently, there is great interest in the development of these peptides as potential drugs for the treatment of drug-resistant infections. However, before these peptides can be used for clinical application, at least two major concerns need to be addressed. First, is there a way to economically generate these peptides? Second, is there enough information to guide the rational design of new peptides with improved selectivity and stability? In regard to the first concern, we believe the difficulties of economical synthesis can be overcome by recombinant production. It is hypothesized that sufficient amounts of highly purified peptides can be obtained using a bacterial expression system and subsequent purification protocols. For the second concern, we believe a peptide database with associated tools is useful in providing such information. It is hypothesized that the content and functions of the existing antimicrobial peptide database (APD) can be greatly improved.

Using LL-37, a member of the abundant class of helical peptides, as an example, I developed a bacterial expression system and three purification protocols for short peptides. Milligrams of highly purified peptide can be obtained from one liter of bacterial culture. This work not only provides sufficient amounts of peptides for routine biological and structural studies but also provides a possible way for industrial scale production of antimicrobial peptides.

For the database development, the content of the APD was updated to include the most recently discovered peptides. To realize new functions, I also redesigned and reimplemented the database. Three new interfaces were added that enhanced the functions of the database. The new database provides more complete statistical data and new tools for rational design of active antibiotics based on naturally occurring antimicrobial peptides.