Unknown

Dataset Information

0

Manipulating the pH response of 2,3-diaminopropionic acid rich peptides to mediate highly effective gene silencing with low-toxicity.


ABSTRACT: Cationic amphipathic pH responsive peptides possess high in vitro and in vivo nucleic acid delivery capabilities and function by forming a non-covalent complex with cargo, protecting it from nucleases, facilitating uptake via endocytosis and responding to endosomal acidification by being released from the complex and inserting into and disordering endosomal membranes. We have designed and synthesised peptides to show how Coulombic interactions between ionizable 2,3-diaminopropionic acid (Dap) side chains can be manipulated to tune the functional pH response of the peptides to afford optimal nucleic acid transfer and have modified the hydrogen bonding capabilities of the Dap side chains in order to reduce cytotoxicity. When compared with benchmark delivery compounds, the peptides are shown to have low toxicity and are highly effective at mediating gene silencing in adherent MCF-7 and A549 cell lines, primary human umbilical vein endothelial cells and both differentiated macrophage-like and suspension monocyte-like THP-1 cells.

SUBMITTER: Abbate V 

PROVIDER: S-EPMC3858832 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

Manipulating the pH response of 2,3-diaminopropionic acid rich peptides to mediate highly effective gene silencing with low-toxicity.

Abbate Vincenzo V   Liang Wanling W   Patel Jayneil J   Lan Yun Y   Capriotti Luigi L   Iacobucci Valentina V   Bui Tam T TT   Chaudhuri Poulami P   Kudsiova Laila L   Vermeer Louic S LS   Chan Patrick F L PF   Kong Xiaole X   Drake Alex F AF   Lam Jenny K W JK   Bansal Sukhvinder S SS   Mason A James AJ  

Journal of controlled release : official journal of the Controlled Release Society 20131018 3


Cationic amphipathic pH responsive peptides possess high in vitro and in vivo nucleic acid delivery capabilities and function by forming a non-covalent complex with cargo, protecting it from nucleases, facilitating uptake via endocytosis and responding to endosomal acidification by being released from the complex and inserting into and disordering endosomal membranes. We have designed and synthesised peptides to show how Coulombic interactions between ionizable 2,3-diaminopropionic acid (Dap) si  ...[more]

Similar Datasets

| S-EPMC3309271 | biostudies-literature
| S-EPMC3309421 | biostudies-literature
| S-EPMC6436733 | biostudies-literature
| S-EPMC3179956 | biostudies-literature
| S-EPMC8246256 | biostudies-literature
| S-EPMC9609037 | biostudies-literature
| S-EPMC6017362 | biostudies-literature
| S-EPMC9459546 | biostudies-literature
| S-EPMC3457398 | biostudies-literature
| S-EPMC7961587 | biostudies-literature