Small but prospective: development of enzyme-responsive small molecule fluorescent probes for specific bacterial imaging

• Main Author: Yan, Evelias Hui Xin
• Other Authors: Xing Bengang
• Format: Thesis-Master by Research
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Chemistry; Fluorescent imaging; Bacterial infections; Small molecules; Enzyme-responsive
• Online Access: https://hdl.handle.net/10356/173983
• Institution: Nanyang Technological University

Bacterial infections remain as a prevailing situation in our today’s society. Owing to the evolving pathogenicity of bacteria, whereby more drug-resistant bacteria has been emerging and bacteria developing their own defense mechanism, traditional antimicrobial approaches like antibiotics treatment have been clinically ineffective. Early and accurate strategies are off dire need to subvert the rapid colonization of bacteria. Hence, the employment of fluorescence imaging for specific bacterial labeling and infection diagnosis could be prospective in providing physiological information in real time for the diagnosis and therapeutic intervention of bacterial infections. Small-molecule fluorescence probes have been an attractive tool in fluorescence imaging due to their inherent properties such as highly tunable emissions, high quantum yield and good biocompatibility. Among the numerous types of small-molecule fluorescence probes, the enzymatic responsive probes have been one that researchers are particularly interested in as such probes were reported to possess great specificity and high signal to noise ratio. Furthermore, bacterial enzymes are found to be closely related to the invasion of host immune system, which makes them a viable target to establish enzyme-activated fluorescent probes for specific bacterial imaging. In chapter 1, we will be giving a brief background on bacterial infections, introducing the principles and techniques used in the design of small-molecule fluorescence probes, and followed by providing some of the reported examples of the recent and typical strategies for enzyme-activated small-molecule fluorescence probes. In chapter 2, we explore the specific proteolytic activity of an outer membrane bacterial protease that is present in all wild-type Escherichia coli (E. coli) and another bacterial protease located in the periplasmic region of E. coli to synthesize a near infrared fluorescence probe for the real-time imaging of urinary tract bacterial infection in vitro and in vivo. In chapter 3, the experimental section and supplementary figures are presented.