Methodologies for the Discovery and Quality Control of Therapeutic Peptides
Choules, Mary Patricia
MetadataShow full item record
This report represents some of the efforts that are part of the research on drug discovery and quality control of therapeutic peptides within the group of Dr. Guido Pauli’s group and the Institute for Tuberculosis Research (ITR). One major aspect of this report covers of the high throughput screening of actinomycete extracts against Mycobacterium tuberculosis by ITR. Through these efforts, a scoring-based prioritization method was developed to assist in the selection of hit actinomycete extracts. This methodology led to the prioritization of an actinomycete strain found to produce the rufomycins (RUFs), a class of highly active cyclic peptides. Full structural and biological characterization of the RUF compounds is presented; including the confirmation of its molecular target, ClpC1. Research pertaining to characterization of ClpC1 as a target as well as its potential in combinatory therapy is also presented. The second major aspect of the report concerns the quality control and quality assurance of peptides. The potential impact quality control can have on drug discovery is demonstrated using two cases of Residual Complexity. To address this issue, a methodology utilizing 1H NMR and 1H iterative Full Spin Analysis was established and developed for adoption in industrial settings.