演題 「Multidisciplinary interrogation of glycobiological processes for novel therapeutics」
講師 Dr. Lingbing Kong，香川大学国際希少糖研究教育機構・助教
要旨 Bacterial drug resistance has been a global grand challenge. Although scientists have endeavored for the last three decades, only a few new antimicrobials are approved by the FDA. I have initiated and led a research program that focused on the interrogation of a transporter of capsular polysaccharides Wza that is conserved in Gram-negative bacteria. Protein engineering of Wza enabled the application of single-molecule electrical channel recording to screen for blockers and understand the bi-molecular interactions at the single-molecule level. Cyclic oligosaccharide am8γCD that binds to the barrel of Wza with nanomolar affinity was discovered. It is non-toxic to the bacteria but it enhances the vulnerability of bacteria to immune attacks by removing the protective capsule layer. A combination of this inhibitor and a synthetic glycoconjugate vaccine based on the lipopolysaccharide has resulted in better immune clearance of bacteria from attacking the host cells. To enable the continual discovery of next-generation of Wza inhibitors, an advanced multidisciplinary single-molecule platform to study the interaction of Wza and its natural substrate K30 polysaccharide fragments has also been established. Furthermore, a novel approach to create monodisperse transmembrane alpha-helical peptide barrels has been developed, based on the C-terminal D4 domain of Wza. Overall, a combination of chemistry, biochemistry, single-molecule biophysics, biology, computation, etc. has been proven a useful and efficient approach to discover novel therapeutics and develop novel biotechnologies.
