The Disputation will be live streamed for everyone else.
The livestream will be activated 15 minutes before the Defense starts.
Trial lecture
September 30th, 10:30 AM, Auditorium 3, Chemistry building
Trial lecture title: Emerging chemical conjugation methods: beyond peptide couplings and click chemistry
Kreeringssammendrag/Conferral summary
Antimikrobiell resistens (AMR) er et pågående problem som krever kontinuerlig utvikling av nye antimikrobielle legemidler. I denne avhandlingen ble det utviklet og testet nye tris(2-pyridylmetyl)amin (TPA)-baserte forbindelser som potensielle AMR-brytere, hvor enkelte TPA-antibiotikum konjugater viste betydelig forbedret effekt sammen med meropenem mot multiresistente Gram-negative bakterier. En ny syntesemetode for kirale β-laktamer ble også utforsket for å bidra til fremtidig antibiotika utvikling.
Main research findings
Antimicrobial resistance (AMR) is a growing global health threat, making it harder to treat infections as bacteria and other microbes become resistant to existing drugs. One promising strategy is to develop “AMR breakers” – compounds that target the resistance mechanisms of these microbes. My thesis focused on tris(2-pyridylmethyl)amine (TPA) compounds as potential AMR breakers.
Two approaches were used to study the effect of TPA agents in combination with common antibiotics: an adjuvant method – mixing a TPA reference with an antibiotic – and a conjugate method – chemically linking TPA with antibiotics. Thirteen novel TPA-functionalized drugs were synthesized. While the adjuvant method showed some promising synergy between TPA reference and antibiotic, the conjugate approach was detrimental to activity against multidrug-resistant (MDR) Gram-negative bacteria. However, when certain TPA-antibiotic conjugates were used alongside the last-resort β-lactam antibiotic meropenem, they significantly enhanced the efficacy of meropenem against MDR Gram-negative bacteria. Some TPA-functionalized drugs even showed direct activity against anaerobic bacteria, Mycobacterium tuberculosis, and fungal species.
Additionally, a new method for synthesizing chiral β-lactams was explored using catalyst-free diazo chemistry. These findings contribute to the ongoing search for new ways to combat AMR and may help guide the development of future antibiotics.
Candidate contact information
LinkedIn: https://www.linkedin.com/in/sara-peeters-martinsen-726337112/
Adjudication committee
Professor Fredrik Almqvist
Umeå University, Sweden
Professor Jørn H. Hansen
The Arctic University of Norway, Norway
Associate Professor Hanne Røberg-Larsen
Department of Chemistry, University of Oslo, Norway
Supervisors
Professor Mats Tilset
Department of Chemistry, University of Oslo, Norway
Associate Professor Tore Bonge-Hansen
Department of Chemistry, University of Oslo, Norway
Associate Professor Pål Rongved
Department of Pharmacy, University of Oslo, Norway
Associate Professor Michele Cascella
Department of Chemistry, University of Oslo, Norway
Chair of defence
Professor Stian Svelle
Department of Chemistry, University of Oslo, Norway