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.
