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Biochemistry

Nor-Pyochelin

Nor-Pyochelin is a chemical derivate of pyochelin, which lacks a single methyl group on its second cyclized cysteine residue. Based on the work of Abdallah et. al., which included a detailed analysis of pyochelin and a couple of similar compounds. We figured that Nor-Pyochelin would outcompete native pyochelin as a potential antibiotic carrier molecule since Abdallah et. Al. measured a 30% higher receptor affinity and iron transport capability for Nor-Pyochelin. An effect that we wanted to replicate in our antibiotic efficiency study.

Nor-Pyochelin

At the beginning of our project we decided that we wanted to do something about multiresistant bacteria that cause lung infections. Therefore, pyochelin, one of two native siderophores of Pseudomonas aeruginosa, became one of our prime targets for bio- and chemical synthesis, as P. aeruginosa is known for its manifold antibiotic resistances and oppurtunistic lung infections. Therefore P. aeruginosa poses a big problem in hospitals as one of the main reasons for opportunistic infections in weakened or immunosuppressed patients. Being extremely resilient and undemanding, pseudomonads are known to survive in hostile environments, like the tubes of breathing devices and even disinfectants, it is hard to prevent pseudomonade infections. Since Pyochelin is relatively small and easy to synthesize, and pseudomonas is one of the most resilient bacteria known, we chose pyochelin as our main target for our trojan horse strategy.

However, fighting pseudomonas with a gallium complex with its native siderophore wasn’t enough. Additionally, during the biobricks design for the pyochelin synthesis we found out that pseudomonas gene sequences consist of a very high GC-content which proved to be very difficult for synthesis and other molecular manipulation. Therefore, we had to design our project towards a similar but different approach. The new target became Nor-Pyochelin.


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