Supplemental Funding Request for Photochemical Electrocyclizations to Virulence Inhibiting Natural Products] Research Strategy Abstract of R01 GM132531-01. Reports of the increasing prevalence of drug resistant bacteria has resulted in a vital need for new strategies for the development of antimicrobials. This application offers such an approach. We plan to take advantage of the enhanced understanding of the role that communication plays in bacterial virulence to develop small molecules that interrupt this phenomenon. Specifically, this work is focused on developing structurally and biologically interesting small molecule natural products from the discorhabdin and abietane families as virulence inhibitors. As part of our effort to generate these families we are developing new chemistry centered around photochemical electrocyclization reactions including enantioselective transformations. Request: We are requesting funds for a Waters Alliance HPLC system (see attached quote). This proposed system would replace our current 15-year old system that has been unusable for the past 1.5 years. Scientific Justification: The work that is currently funded by this grant is dependent upon our being able to generate single component small molecule analogs of the discorhabdin and abietane families that are also optically pure. This is due to it being critical that we know the precise composition of everything that bring into antibacterial bioassays and for the reproducibility of both the assays and the synthesis. One of the most accurate means of determining purity is via HPLC, hence this supplemental request. Ready access to this instrument will make it much easier to determine the purity, including the optical purity, of our synthetic samples and allow us to more rapidly make decisions about research directions. Why the equipment was not anticipated: At the time that we submitted this grant application our previous HPLC was still working. We thought that we would be able to continue using the old instrument but it turns out that its repair would not be cost effective (one estimate puts the cost of repair at $20,000). Our research program simply has not had the funding to make this sort of purchase over the past several years. Routine training and maintenance: Waters fully supports their instruments and will provide training. The Waters technician (Denise Kent) is regularly on the University of Utah campus at our Mass Spectrometry facility. Our initial training will be provided by Waters; subsequently a group member will be put in charge of routine maintenance and training-we will follow Waters? recommendations for routine maintenance. Timeline for installation and operation: Waters promises to install the instrument within 30 days of it being ordered. We anticipate it being fully operational within one week after that. Thus, the instrument will be ready to use within 45 days of this supplemental request being granted.
Supplemental Funding Request for Photochemical Electrocyclizations to Virulence Inhibiting Natural Products Budget Justification Availability of Funds from Current Award: We are requesting funds for a Waters Alliance HPLC system (ca. $48,000). While we will purchase all of the necessary normal and reverse phase columns with funds from the current award (ca. $12,000 of the $48,000), we do not have sufficient unobligated funds from the current award to make the entire purchase; we have ca. $6000 in unobligated funds from the 2019-2020 funding year. We could make this purchase by freeing up salary but this would require that we cut back on our aims for the coming year. Availability of Funds from Institution and other Support: The University of Utah does not have a mechanism in place to support this purchase. The quoted cost of the HPLC ($35,218.80) is discounted according to the Waters Technologies Corporation (list price of $88,048.00). As mentioned above, we will use $12,000 of our current award to purchase the necessary columns for the instrument. Extended Warranty/Maintenance Contract: The PI will use his revolving funds (ca. $5000/year) to purchase the extended warranty and necessary maintenance contract. Multiple Awardees/Shared Equipment: NA
