We would like to thank Xianwen Lou for GPC analysis and Biomedal S.L. for supplying the pALEX2-Ca-GFP plasmid to produce C-Lyt-GFP. This work was supported by a VIDI grant from the Netherlands Organisation for Scientific Research (grant 700.56.428), the Escuela Valenciana de Estudios para la Salud (Generalidad Valenciana, Spain, Grant 95/2005) and the Fundación Salvat Inquifarma (Spain). Ciber de Enfermedades Respiratorias (CibeRes) is an initiative of Spanish Instituto de Salud Carlos III. Additional funding was provided by the COMBACT program (S-BIO-0260/2006) of the Comunidad de Madrid. V.M.H.-R. was supported by a PhD fellowship from Spanish Ministry of Education.
1521-3773/asset/2002_left.gif?v=1&s=ac6b0d94a94d7ce7a210002b8096b42feffc0bcf)
1521-3773/asset/2002_right.gif?v=1&s=451042aa3415ae3ad0729984d26dee1866aca82e)
Communication
Multivalent Choline Dendrimers as Potent Inhibitors of Pneumococcal Cell-Wall Hydrolysis†
Article first published online: 29 DEC 2008
DOI: 10.1002/anie.200803664
Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Hernández-Rocamora, V., Maestro, B., de Waal, B., Morales, M., García, P., Meijer, E., Merkx, M. and Sanz, J. (2009), Multivalent Choline Dendrimers as Potent Inhibitors of Pneumococcal Cell-Wall Hydrolysis. Angewandte Chemie International Edition, 48: 948–951. doi: 10.1002/anie.200803664
- †
Publication History
- Issue published online: 13 JAN 2009
- Article first published online: 29 DEC 2008
- Manuscript Revised: 14 OCT 2008
- Manuscript Received: 27 JUL 2008
Funded by
- Netherlands Organisation for Scientific Research. Grant Number: 700.56.428
- Escuela Valenciana de Estudios para la Salud. Grant Number: 95/2005
- Fundación Salvat Inquifarma. Grant Number: S-BIO-0260/2006
- Comunidad de Madrid
Keywords:
- antimicrobial agents;
- dendrimers;
- inhibitors;
- medicinal chemistry;
- multivalency
Graphical Abstract
Dendritic cell-wall mimics: Choline-binding proteins from Streptococcus pneumoniae recognize distinctive multivalent choline architectures on the bacterial cell wall. Choline-functionalized dendrimers are potent inhibitors of these essential enzymes, with a 103–104-fold higher affinity than free choline, resulting in inhibition of autolysis and cell separation in bacterial cultures at low micromolar concentrations (see picture).