SBIR-STTR Award

In this Small Business Innovation Research Phase I project a unique approach is used to produce analogs of antibiotics belonging to the family of antibiotics called lantibiotics using a technology referred to as Differentially Protected Orthogonal Lanthionine Technology (DPOLT). Attempts to study lantibiotics for their potential usefulness in therapeutic applications have been hindered by the difficulty of obtaining them in sufficient amounts or with sufficient purity to enable the required testing. In this proposal lantibiotic nisin is synthesized as an initial proof of principal for DPOLT. Many strains of medically important bacteria have become increasingly resistant to antibiotics used in the treatment of clinical infections. Thus, there is a pressing need for the development of new antibiotics. There is a class of small, peptide antibiotics called lantibiotics that are defined by the presence of unusual amino acids, notably lanthionine (Lan) and methyllanthionine (MeLan). Lantibiotics that have been studied indicate that they typically are potent antibacterials and have a broad spectrum of activity, notably against gram positive species. The technology depends on the bulk manufacture of two separate lanthionine moieties whose active carboxyl and amino groups are protected with groups that can be differentially removed. The differentially protected lanthionines can also be used in solid state synthesis with minimal changes in the routine methods employed for the cost effective manufacture of a number of commercially available bioactive peptides

The Small Business Innovation Research (SBIR) Phase II project aims to develop differentially protected orthogonal lanthionine technology (DPLOT) to synthesize novel antibiotics. Lanthionines are found in nature and have been isolated from a variety of sources. Although amino acids, lanthionines are not components of proteins. They are however, constituents of a group of naturally occurring peptide antibiotics called lantibiotics, which includes nisin (a food preservative), subtilin, epidermin (an anti staphylococcus and streptococcus agent), and ancovenin (an enzyme inhibitor). Due to their mechanism of action, resistance to lantibiotics is uncommon and as such they can be of value for treating antibiotic resistant bacterial infections. The technology under development would allow the synthesis of novel lantibiotics that may be effective against the growing number of antibiotic resistant bacteria and would expand the therapeutic arsenal available for treating such infections. It would therefore have a profound impact on public health and the control of infectious diseases caused by bacteria