Evaluation of the Stereochemistry of Staphyloferrin A for Developing Staphylococcus‐Specific Targeting Conjugates

• Published in: Chembiochem : a European journal of chemical biology 2024-09, Vol.25 (18), p.e202400480-n/a
• Main Authors: Wang, Tsung‐Shing Andrew, Chen, Pin‐Lung, Chen, Yi‐Chen Sarah, Chiu, Yu‐Wei, Lin, Zih‐Jheng, Kao, Chih‐Yao, Hung, Hsuan‐Min
• Format: Article
• Language: English
• Subjects: Amino acids; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Citrates - chemistry; Click chemistry; Conjugates; Drug resistance; Fluorescence; Fluorescent Dyes - chemistry; Fluorescent indicators; Humans; Methicillin; Microbial Sensitivity Tests; Molecular Structure; Ornithine - analogs & derivatives; Ornithine - chemistry; Pharmacology; Probes; Public health; Selective bacterial targeting; Siderophore; Staphylococcus; Staphylococcus bacteria; Staphyloferrin A; Stereochemistry; Stereoisomerism; Vancomycin
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202400480

Bacteria in the genus Staphylococcus are pathogenic and harmful to humans. Alarmingly, some Staphylococcus, such as methicillin‐resistant S. aureus (MRSA) and vancomycin‐resistant S. aureus (VRSA) have spread worldwide and become notoriously resistant to antibiotics, threatening and concerning public health. Hence, the development of new Staphylococcus‐targeting diagnostic and therapeutic agents is urgent. Here, we chose the S. aureus‐secreted siderophore staphyloferrin A (SA) as a guiding unit. We developed a series of Staphyloferrin A conjugates (SA conjugates) and showed the specific targeting ability to Staphylococcus bacteria. Furthermore, among the structural factors we evaluated, the stereo‐chemistry of the amino acid backbone of SA conjugates is essential to efficiently target Staphylococci. Finally, we demonstrated that fluorescent Staphyloferrin A probes (SA‐FL probes) could specifically target Staphylococci in complex bacterial mixtures. Among several structural factors of siderophore staphyloferrin A (SA), the stereochemistry of the amino acid backbone is essential for efficiently targeting Staphylococci. Utilizing the observed stereochemistry‐labeling relationship, several SA‐fluorophore conjugates were developed to achieve Staphylococcus‐specific targeting and labeling.