Presentation Type

Poster Presentation

Faculty Mentor’s Full Name

Nigel Priestley

Category

STEM (science, technology, engineering, mathematics)

Abstract/Artist Statement

Introduction of new antibiotics into the market is important and urgent. Over the past decade there have been few novel antibiotics and cases of antimicrobial resistance infections is expected to increase. Most antibiotics have been developed with structure-based drug design of known target mechanisms, or from natural products. The limit of using natural products is that many are already diverse and complex in structure and have limited synthetic flexibility. Fragments of natural products are more synthetically pliable and can be linked together similar to amino acids in peptide synthesis. An in-slica library of natural product fragment reassembly (NPFR) would provide a diverse selection of new structures that overlap traditional natural product classes. This more diverse library will have a higher hit-rate for potential new antimicrobial drugs unlike traditional market available libraries. A representative selection of 64 in-slica compounds will be synthesized and assayed for antimicrobial activity through minimum inhibitory concentration levels. The activity of the NPFR selection will represent the NPRF library compared with the hit-rate of traditional market available libraries.

Mentor Name

Nigel Priestley

Personal Statement

A challenge in drug discovery is finding a sources for new drugs, and many have come from either known natural products or computer-generated libraries. The natural product fragment reassembly focus is not much on the creation of a new source but rather refining the process in which we select compounds to represent a library. Generated libraries can have infinite number of novel compounds, but different factors are taken in consideration of selection. The most common technique is placing filters over the libraries. These filters can be restraints for or removal of specific structural traits. Synthesis is the next consideration for how many steps it may need to reach the desired compound, or the cost of the materials and time for synthesis. As a student have been primarily focused on the individual synthetic routes pre-selected compounds but never had to select the compounds personally from a new library. This project is helping broaden my view and learn more about synthetic library formations and the selection process for compounds. This is to help refine my own ability to select and propose new bio-active structure candidates in a more organized fashion, instead of randomly selecting compounds till there is a bio-active hit. My future goal is to graduate and continue synthesis work in the drug development field. If assigned several compounds I can learn to prioritize the list using the various selection process, and reach the potentially bio-active compounds earlier rather than later. This will boost efficiency of both time, materials, and reaching new treatment options for patients. The diverse sampling would also indicate the likelihood of a favorable outcomes from a library set. Even if the library may be large, if all the compounds have high similarities there would be minimal chance of latter list compounds to exhibit bio-active traits unlike a smaller library with less similarity between candidates.

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Mar 4th, 5:00 PM Mar 4th, 6:00 PM

High Potential Antimicrobial Hit-Rate of a Natural Product Fragment Reassembly Library

UC North Ballroom

Introduction of new antibiotics into the market is important and urgent. Over the past decade there have been few novel antibiotics and cases of antimicrobial resistance infections is expected to increase. Most antibiotics have been developed with structure-based drug design of known target mechanisms, or from natural products. The limit of using natural products is that many are already diverse and complex in structure and have limited synthetic flexibility. Fragments of natural products are more synthetically pliable and can be linked together similar to amino acids in peptide synthesis. An in-slica library of natural product fragment reassembly (NPFR) would provide a diverse selection of new structures that overlap traditional natural product classes. This more diverse library will have a higher hit-rate for potential new antimicrobial drugs unlike traditional market available libraries. A representative selection of 64 in-slica compounds will be synthesized and assayed for antimicrobial activity through minimum inhibitory concentration levels. The activity of the NPFR selection will represent the NPRF library compared with the hit-rate of traditional market available libraries.