tetano
Editor, Senior Moderator
Molecules. 2019 May 31;24(11). pii: E2079. doi: 10.3390/molecules24112079.
[h=1]Novel pH Selective, Highly Lytic Peptides Based on a Chimeric Influenza Hemagglutinin Peptide/Cell Penetrating Peptide Motif.[/h] Algayer B[SUP]1[/SUP], O'Brien A[SUP]2[/SUP], Momose A[SUP]3[/SUP], Murphy DJ[SUP]4[/SUP], Procopio W[SUP]5[/SUP], Tellers DM[SUP]6[/SUP], Tucker TJ[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Delivery of macromolecular cargos such as siRNA to the cytosol after endocytosis remains a critical challenge. Numerous approaches including viruses, lipid nanoparticles, polymeric constructs, and various peptide-based approaches have yet to yield a general solution to this delivery issue. In this manuscript, we describe our efforts to design novel endosomolytic peptides that could be used to facilitate the release of cargos from a late endosomal compartment. These amphiphilic peptides, based on a chimeric influenza hemagglutinin peptide/cell-penetrating peptide (CPP) template, utilize a pH-triggering mechanism in which the peptides are protonated after acidification of the endosome, and thereby adopt an alpha-helical conformation. The helical forms of the peptides are lytically active, while the non-protonated forms are much less or non-lytically active at physiological pH. Starting from an initial lead peptide (INF7-Tat), we systematically modified the sequence of the chimeric peptides to obtain peptides with greatly enhanced lytic activity that maintain good pH selectivity in a red blood cell hemolysis assay.
[h=4]KEYWORDS:[/h] RBC lysis; amphiphilic; endosomolytic; fusogenic; influenza hemagglutinin; peptides
PMID: 31159194 DOI: 10.3390/molecules24112079
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[h=1]Novel pH Selective, Highly Lytic Peptides Based on a Chimeric Influenza Hemagglutinin Peptide/Cell Penetrating Peptide Motif.[/h] Algayer B[SUP]1[/SUP], O'Brien A[SUP]2[/SUP], Momose A[SUP]3[/SUP], Murphy DJ[SUP]4[/SUP], Procopio W[SUP]5[/SUP], Tellers DM[SUP]6[/SUP], Tucker TJ[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Delivery of macromolecular cargos such as siRNA to the cytosol after endocytosis remains a critical challenge. Numerous approaches including viruses, lipid nanoparticles, polymeric constructs, and various peptide-based approaches have yet to yield a general solution to this delivery issue. In this manuscript, we describe our efforts to design novel endosomolytic peptides that could be used to facilitate the release of cargos from a late endosomal compartment. These amphiphilic peptides, based on a chimeric influenza hemagglutinin peptide/cell-penetrating peptide (CPP) template, utilize a pH-triggering mechanism in which the peptides are protonated after acidification of the endosome, and thereby adopt an alpha-helical conformation. The helical forms of the peptides are lytically active, while the non-protonated forms are much less or non-lytically active at physiological pH. Starting from an initial lead peptide (INF7-Tat), we systematically modified the sequence of the chimeric peptides to obtain peptides with greatly enhanced lytic activity that maintain good pH selectivity in a red blood cell hemolysis assay.
[h=4]KEYWORDS:[/h] RBC lysis; amphiphilic; endosomolytic; fusogenic; influenza hemagglutinin; peptides
PMID: 31159194 DOI: 10.3390/molecules24112079
Free full text