4.7 Article

Carbosilane Dendron-Peptide Nanoconjugates as Antimicrobial Agents

Journal

MOLECULAR PHARMACEUTICS
Volume 16, Issue 6, Pages 2661-2674

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.9b00222

Keywords

antibacterial peptides; carbosilane dendrons; molecular modeling and molecular dynamics

Funding

  1. MINECO [CTQ2017-86224-P]
  2. Consortium NANODENDMED II-CM [B2017/BMD-3703]
  3. Consortium IMMUNOTHERCAN-CM [B2017/BMD-3733]
  4. Spanish Ministerio de Economia, Industria y Competitividad [SAF2014-60138-R]
  5. FEDER funds
  6. Generalitat de Catalunya [2017SGR1439]
  7. ERDF/ESF project UniQSurf-Centre of Biointerfaces and Hybrid Functional Materials [CZ.02.1.01/0.0/0.0/17_048/0007411]
  8. Research Infrastructure NanoEnviCz
  9. Ministry of Education, Youth and Sports of the Czech Republic [LM2015073]
  10. VI National R-D-i Plan 2008-2011
  11. Iniciativa Ingenio 2010
  12. Consolider Program
  13. CIBER Actions
  14. Instituto de Salud Carlos III
  15. Ministerio de Economia y Competitividad

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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 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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