TY  - JOUR
AU  - Xu, Maokai
AU  - Antonova, Maria
AU  - Salavei, Pavel
AU  - Illek, Katharina
AU  - Meléndez, Ana Valeria
AU  - Omidvar, Ramin
AU  - Thuenauer, Roland
AU  - Makshakova, Olga
AU  - Roemer, Winfried
TI  - Dimeric Lectin Chimeras as Novel Candidates for Gb3-Mediated Transcytotic Drug Delivery through Cellular Barriers
JO  - Pharmaceutics
VL  - 15
IS  - 1
SN  - 1999-4923
CY  - Basel
PB  - MDPI
M1  - PUBDB-2024-05772
SP  - 225 
PY  - 2023
AB  - Receptor-mediated transcytosis is an elegant and promising strategy for drug delivery across biological barriers. Here, we describe a novel ligand–receptor pair based on a dimeric, engineered derivative of the Pseudomonas aeruginosa lectin LecA, here termed Di-LecA, and the host cell glycosphingolipid Gb3. We characterized the trafficking kinetics and transcytosis efficiencies in polarized Gb3-positive and -negative MDCK cells using mainly immunofluorescence in combination with confocal microscopy. To evaluate the delivery capacity of dimeric LecA chimeras, EGFP was chosen as a fluorescent model protein representing macromolecules, such as antibody fragments, and fused to either the N- or C-terminus of monomeric LecA using recombinant DNA technology. Both LecA/EGFP fusion proteins crossed cellular monolayers in vitro. Of note, the conjugate with EGFP at the N-terminus of LecA (EGFP-LecA) showed a higher release rate than the conjugate with EGFP at the C-terminus (LecA-EGFP). Based on molecular dynamics simulations and cross-linking studies of giant unilamellar vesicles, we speculate that EGFP-LecA tends to be a dimer while LecA-EGFP forms a tetramer. Overall, we confidently propose the dimeric LecA chimeras as transcytotic drug delivery tools through Gb3-positive cellular barriers for future in vivo tests.Keywords:Gb3-binding lectin; glycosphingolipid; transcytosis; drug carrier; protein engineering; protein structure; valency; accelerated molecular dynamics 
LB  - PUB:(DE-HGF)16
C6  - pmid:36678854
UR  - <Go to ISI:>//WOS:000918781700001
DO  - DOI:10.3390/pharmaceutics15010225
UR  - https://bib-pubdb1.desy.de/record/614232
ER  -