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Carbosilane Dendron-Peptide Nanoconjugates as Antimicrobial Agents

J. Fernandez, G. Acosta, D. Pulido, M. Malý, JL. Copa-Patiño, J. Soliveri, M. Royo, R. Gómez, F. Albericio, P. Ortega, FJ. de la Mata,

. 2019 ; 16 (6) : 2661-2674. [pub] 20190430

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc20006437

Over the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective antimicrobial molecules. On the one hand, antimicrobial peptides (AMPs) are regarded as good alternatives because of their generally broad-spectrum activities, but sometimes they can be easily degraded by the organism or be toxic to animal cells. On the other hand, cationic carbosilane dendrons, whose focal point can be functionalized in many different ways, have also shown good antimicrobial activity. In this work, we synthetized first- and second-generation cationic carbosilane dendrons with a maleimide molecule on their focal point, enabling their functionalization with three different AMPs. After different microbiology studies, we found an additive effect between first-generation dendron and AMP3 whose study reveals three interesting effects: (i) bacteria aggregation due to AMP3, which could facilitate bacteria detection or even contribute to antibacterial activity by preventing host cell attack, (ii) bacteria disaggregation capability of second-generation cationic dendrons, and (iii) a higher AMP3 aggregation ability when dendrons were added previously to peptide treatment. These compounds and their different effects observed over bacteria constitute an interesting system for further mechanism studies.

Citace poskytuje Crossref.org

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$a Fernandez, Jael $u Instituto de Investigación Química "Andrés M. del Río" (IQAR) , UAH , 28801 Alcalá de Henares , Spain. Networking Research Center on Bioengineering , Biomaterials and Nanomedicine (CIBER-BBN) , 28029 Madrid , Spain. Instituto Ramón y Cajal de Investigación Sanitaria, IRYCIS , 28034 Madrid , Spain.
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$a Over the last decades, multidrug-resistant bacteria have emerged and spread, increasing the number of bacteria, against which commonly used antibiotics are no longer effective. It has become a serious public health problem whose solution requires medical research in order to explore novel effective antimicrobial molecules. On the one hand, antimicrobial peptides (AMPs) are regarded as good alternatives because of their generally broad-spectrum activities, but sometimes they can be easily degraded by the organism or be toxic to animal cells. On the other hand, cationic carbosilane dendrons, whose focal point can be functionalized in many different ways, have also shown good antimicrobial activity. In this work, we synthetized first- and second-generation cationic carbosilane dendrons with a maleimide molecule on their focal point, enabling their functionalization with three different AMPs. After different microbiology studies, we found an additive effect between first-generation dendron and AMP3 whose study reveals three interesting effects: (i) bacteria aggregation due to AMP3, which could facilitate bacteria detection or even contribute to antibacterial activity by preventing host cell attack, (ii) bacteria disaggregation capability of second-generation cationic dendrons, and (iii) a higher AMP3 aggregation ability when dendrons were added previously to peptide treatment. These compounds and their different effects observed over bacteria constitute an interesting system for further mechanism studies.
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$a Acosta, Gerardo $u Networking Research Center on Bioengineering , Biomaterials and Nanomedicine (CIBER-BBN) , 28029 Madrid , Spain. Deparment of Organic and Inorganic Chemistry , University of Barcelona , 08028 Barcelona , Spain. Institute for Advanced Chemistry of Catalonia-CSIC , 08034 Barcelona , Spain.
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