Multivalent dendritic molecules as broad spectrum bacteria agglutination agents.
This study reports the first set of synthetic molecules that act as broad spectrum agglutination agents and thus are complementary to the specific targeting of antibodies. The molecules have dendritic architecture and contain multiple copies of zinc(II)-dipicolylamine (ZnDPA) units that have selective affinity for the bacterial cell envelope. A series of molecular structures were evaluated, with the number of appended ZnDPA units ranging from four to thirty-two. Agglutination assays showed that the multivalent probes rapidly cross-linked ten different strains of bacteria, regardless of Gram-type and cell morphology. Fluorescence microscopy studies using probes with four ZnDPA units indicated a high selectivity for bacteria agglutination in the presence of mammalian cells and no measurable effect on the health of the cells. The high bacterial selectivity was confirmed by conducting in vivo optical imaging studies of a mouse leg infection model. The results suggest that multivalent ZnDPA molecular probes with dendritic structures have great promise as selective, broad spectrum bacterial agglutination agents for infection imaging and theranostic applications.
Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA.
Shuzhang
S
Xiao
Lica
L
Abu-Esba
Serhan
S
Turkyilmaz
Alexander G
AG
White
Bradley D
BD
Smith
D000372:Agglutination Tests; D000588:Amines / Q000378:metabolism*; D000818:Animals; D001419:Bacteria / Q000737:chemistry* / Q000378:metabolism*; D001424:Bacterial Infections / Q000175:diagnosis / Q000382:microbiology; D003952:Diagnostic Imaging / Q000379:methods; D004195:Disease Models, Animal; D005456:Fluorescent Dyes / Q000737:chemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D061848:Optical Imaging / Q000379:methods; D010848:Picolinic Acids / Q000378:metabolism*; D013194:Staining and Labeling / Q000379:methods*; D015032:Zinc / Q000378:metabolism*
C501847:2,2'-dipicolylamine; D000588:Amines; D005456:Fluorescent Dyes; D010848:Picolinic Acids; D015032:Zinc
agglutination; bacteria; molecular imaging; multivalency; zinc(II)-dipicolylamine.