University of Alberta Department of Chemistry 8QLYHUVLW\ RI $OEHUWD 'HSDUWPHQW RI &KHPLVWU\ ZZZFKHPXDOEHUWDFD JV/bg E3-47A; ext: 780 492 3477 Organic Division Invited Speaker Karine Auclair Professor, Department of Chemistry McGill University will speak on “Using the CoA biosynthetic pathway in the activation of antimicrobial agents” This presentation will discuss three different strategies to tackle the problem of antimicrobial drug resistance, each taking advantage of the CoA biosynthetic pathway to activate prodrugs inside the pathogen. According to the WHO, antibiotic resistance has become such a pressing issue that humanity may regress into a post-antibiotic era where “things as common as strep throat or a child’s scratched knee could once again kill”. One of our targets is an antibiotic resistance-causing enzyme: aminoglycoside 6’-N-acetyltransferase (AAC6’). Expression of AAC6’ by bacteria renders them resistant to almost all aminoglycoside antibiotics. We have designed pantothenate derivatives which in bacteria, are transformed into nanomolar inhibitors of AAC6’ by the CoA biosynthetic pathway, and resensitize resistant bacteria to aminoglycoside antibiotics. Our second strategy involves the design of new pantothenate derivatives/mimics as potential new antibacterial or antiplasmodial agents. These molecules may act as CoA antimetabolites after bioactivation by CoA biosynthetic enzymes. Finally, our third target is the itaconate degradation pathway. Here again, our inhibitors are built from a pantothenate derivatives by three enzymes of the CoA biosynthetic pathway inside bacteria. Interestingly, although inhibition of itaconate degradation is innocuous under nutrient-rich conditions, it is lethal in poor media such as that within activated macrophages. This strategy may find use to resensitize some intracellular pathogens to the host immune system and treat infections with minimal selection for resistance. Overall this presentation will include medicinal chemistry with a strong emphasis on biological mechanisms. DATE: Wed., 14 June 2017 TIME: 11:00 a.m. PLACE: CCIS 1-140 Chemistry Notices For the Week of June 12 to June 16, 2017 Submissions: Please send to [email protected]by Wednesday for the following week’s edition VISITING SPEAKERS AND SEMINARS University of Alberta Department of Chemistry 8QLYHUVLW\ RI $OEHUWD 'HSDUWPHQW RI &KHPLVWU\ ZZZFKHPXDOEHUWDFD DH/ce E3-47; ext: 780 492 0055 Chemical Biology Division Student Invited Speaker Dr. Bradley Pentelute MIT Chemistry Cysteine arylation to design and discover proteins Abstract: Here we report a robust bioconjugation method using cysteine arylation. This chemistry enables site- specific conjugation at cysteine residues within peptides, proteins, and antibodies. Our two developed approaches use either perfluoroaryl-cysteine SNAr chemistry or organometallic palladium reagents. This work lead to the discovery of a self-labeling four-residue sequence that enables regioselective conjugation at only one cysteine residue within an intact antibody containing natural amino acids. Recently, we discovered a new approach for the native conjugation of complex natural products such as vancomycin onto peptides and proteins without the introduction of linkers or chemical handles. DATE: Monday June 12, 2017 TIME: 11:00 a.m PLACE: E1-60 Gunning/Lemieux Chemistry Centre Eva M. RodriguezLopez Ph.D Seminar will speak on “Synthesis of biosynthetic intermediates of Tabtoxin, and Inhibition studies of DapL” Wednesday, June 14, 2017 2:00 p.m. in Chemistry Centre Room E325
“Using the CoA biosynthetic pathway in the activation of antimicrobial agents”
This presentation will discuss three different strategies to tackle the problem of antimicrobial drug resistance, each taking advantage of the CoA biosynthetic pathway to activate prodrugs inside the pathogen. According to the WHO, antibiotic resistance has become such a pressing issue that humanity may regress into a post-antibiotic era where “things as common as strep throat or a child’s scratched knee could once again kill”. One of our targets is an antibiotic resistance-causing enzyme: aminoglycoside 6’-N-acetyltransferase (AAC6’). Expression of AAC6’ by bacteria renders them resistant to almost all aminoglycoside antibiotics. We have designed pantothenate derivatives which in bacteria, are transformed into nanomolar inhibitors of AAC6’ by the CoA biosynthetic pathway, and resensitize resistant bacteria to aminoglycoside antibiotics. Our second strategy involves the design of new pantothenate derivatives/mimics as potential new antibacterial or antiplasmodial agents. These molecules may act as CoA antimetabolites after bioactivation by CoA biosynthetic enzymes. Finally, our third target is the itaconate degradation pathway. Here again, our inhibitors are built from a pantothenate derivatives by three enzymes of the CoA biosynthetic pathway inside bacteria. Interestingly, although inhibition of itaconate degradation is innocuous under nutrient-rich conditions, it is lethal in poor media such as that within activated macrophages. This strategy may find use to resensitize some intracellular pathogens to the host immune system and treat infections with minimal selection for resistance. Overall this presentation will include medicinal chemistry with a strong emphasis on biological mechanisms.
Cysteine arylation to design and discover proteins
Abstract: Here we report a robust bioconjugation method using cysteine arylation. This chemistry enables site-specific conjugation at cysteine residues within peptides, proteins, and antibodies. Our two developed approaches use either perfluoroaryl-cysteine SNAr chemistry or organometallic palladium reagents. This work lead to the discovery of a self-labeling four-residue sequence that enables regioselective conjugation at only one cysteine residue within an intact antibody containing natural amino acids. Recently, we discovered a new approach for the native conjugation of complex natural products such as vancomycin onto peptides and proteins without the introduction of linkers or chemical handles.
DATE: Monday June 12, 2017 TIME: 11:00 a.m PLACE: E1-60 Gunning/Lemieux Chemistry Centre
Eva M. Rodriguez-‐Lopez
Ph.D Seminar
will speak on
“Synthesis of biosynthetic intermediates of Tabtoxin, and
Inhibition studies of DapL”
Wednesday, June 14, 2017 2:00 p.m. in Chemistry Centre
Room E3-‐25
EMPLOYMENT OPPORTUNITIES
EMPLOYMENT OPPORTUNI
Assistant Teaching Professor of Chemistry
The Department of Chemistry at the University of Victoria invites applications for an Assistant Teaching Professor with expertise in the area of Organic Chemistry. The successful candidate will be responsible for teaching organic and bioorganic chemistry courses at the second and third year level and may be required to teach chemistry at other levels. The appointee will become an outstanding teacher and mentor of undergraduate students, and will contribute to the development and delivery of core programs in Chemistry. The Department of Chemistry is a research-intensive unit at the University of Victoria and is dedicated to providing outstanding programs for undergraduate students in Chemistry. Graduates of the department are well prepared for graduate school, professional programs and positions in the private sector. Recent enhancement of research activities within the department, as well as increases in the number of graduate students and undergraduate students, characterise the department as one of the strongest in Canada. New research space and undergraduate laboratory space has dramatically enhanced research activity and the laboratory experience for undergraduate students. The Department of Chemistry is highly collegial and benefits from the services of a very effective and dedicated staff. REQUIREMENTS The successful candidate will have: PhD in Chemistry or a relevant discipline, Teaching experience at the university level, Demonstrated interest in a career in teaching, Outstanding ability in teaching chemistry courses with potential to teach at all levels, Ability to teach in areas of organic, biological and general chemistry, Compatibility with the Department of Chemistry at UVic, including ability to interact with the members of the
department, Potential for initiating development of the curriculum and delivery of the academic program. APPLICATION INSTRUCTIONS Applicants should provide: a cover letter, a curriculum vitae, a teaching dossier including a philosophy that reflects a demonstrated commitment to a career in teaching, names and contact information for three or more individuals able to act as referees. Documents should be sent to Sandra Carlson, Department Secretary, Department of Chemistry, University of Victoria, PO Box 1700 STN CSC, Victoria BC V8W 2Y2 Canada, [email protected]. Applications will be considered after 1 August 2017 for potential appointment on 1 January 2018. Faculty and Librarians at the University of Victoria are governed by the provisions of the Collective Agreement. Members are represented by the University of Victoria Faculty Association (http://uvicfa.ca). The University of Victoria is an equity employer and encourages applications from women, persons with disabilities, visible minorities, aboriginal peoples, people of all sexual orientations and genders, and others who may contribute to the further diversification of the university. All qualified individuals are encouraged to apply however in accordance with Canadian immigration requirements, Canadian citizens and permanent residents will be given priority.
