Internalization of cationic peptides: the road less (or more?) traveled

Fuchs, Stephen M.; Raines, Ronald T.

doi:10.1007/s00018-006-6170-z

Cited by 88 publications

(101 citation statements)

References 40 publications

(40 reference statements)

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“…Electrostatic interactions are favored by the presence of two Arg residues, an aminoacid that is present in many AMPs due to its strong interaction with PG headgroups [19,20]. It is well known that the increase in hydrophobicity obtained from fatty acid acylation of AMPs increases antimicrobial activity by favoring the interaction with the lipid membrane [44].…”

Section: Discussionmentioning

confidence: 99%

“…1) maintains the characteristics of PxB that are important for antibacterial activity, such as a cyclic nature, an overall positive charge, and an amphipathic structure, with two hydrophobic domains: a fatty acid in the N-terminus and two hydrophobic aminoacids in position 6-7 of the cycle. In this analog, some of the natural Dab residues of PxB have been substituted by Arg, another basic and positively charged aminoacid that is known to interact more strongly with the anionic membranes due to the particular properties of the guanidine group, providing arginine with strong bidentate cationic character and hydrogen-bond forming properties [19]. This allows arginine to form cation-interactions that make insertion into the hydrophobic core of the bilayer energetically more favorable [20].…”

Section: Introductionmentioning

confidence: 99%

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Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Grau-Campistany

Pujol

Marqués

et al. 2015

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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ARTICLE IN PRESS• Sp-85 is a new synthetic antibiotic lipopeptide with broad spectrum activity.• Pressure-area curves of mixed monolayers show non-ideal mixing.• Binding to anionic liposomes results in fusion and leakage of aqueous contents.• TEM images of antibiotic-exposed bacteria show damaged membranes.• A mechanism of action based on bacterial membrane destabilization is proposed.g r a p h i c a l a b s t r a c t a r t i c l e i n f o a b s t r a c tAntimicrobial peptides offer a new class of therapeutic agents to which bacteria may not be able to develop genetic resistance, since their main activity is in the lipid component of the bacterial cell membrane. We have developed a series of synthetic cationic cyclic lipopeptides based on natural polymyxin, and in this work we explore the interaction of sp-85, an analog that contains a C12 fatty acid at the N-terminus and two residues of arginine. This analog has been selected from its broad spectrum antibacterial activity in the micromolar range, and it has a disruptive action on the cytoplasmic membrane of bacteria, as demonstrated by TEM. In order to obtain information on the interaction of this analog with membrane lipids, we have obtained thermodynamic parameters from mixed monolayers prepared with POPG and POPE/POPG (molar ratio 6:4), as models of Gram positive and Gram negative bacteria, respectively. Langmuir-Blodgett films have been extracted on glass plates and observed by confocal microscopy, and images are consistent with a strong destabilizing effect on the membrane organization induced by sp-85. The effect of sp-85 on the membrane is confirmed with unilamelar lipid vesicles of the same composition, where biophysical experiments based on fluorescence are indicative of membrane fusion and permeabilization starting at very low concentrations of peptide and only if anionic lipids are present. Overall, results described here provide strong evidence that the mode of action of sp-85 is the alteration of the bacterial membrane permeability barrier.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Grau-Campistany

Pujol

Marqués

et al. 2015

Colloids and Surfaces A: Physicochemical and Engineering Aspect

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“…[41][42][43][44][45][46][47][48][49][50] On the basis of these past reports and the results of our current study, we sought to determine whether ultrathin multilayered RNase A-R 9 /SPS films could be used to promote the surface-mediated delivery of RNase A to cells.…”

Section: Surface-mediated Delivery Of Rnase A-r 9 To Cellsmentioning

confidence: 99%

Multilayered Films Fabricated from an Oligoarginine-Conjugated Protein Promote Efficient Surface-Mediated Protein Transduction

et al. 2007

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The conjugation of cationic protein transduction domains to proteins results in an increase in the extent to which proteins are internalized by cells. This investigation sought to determine whether the conjugation of a protein transduction domain to a functional protein could be used to facilitate the incorporation of the protein into multilayered polyelectrolyte films and, subsequently, whether these films could be used to promote surface-mediated protein transduction. We demonstrate that it is possible to fabricate multilayered assemblies 80 nm thick using sodium polystyrene sulfonate (SPS) and bovine pancreatic ribonuclease (RNase A) conjugated to the cationic protein transduction domain nonaarginine (R 9 ) using an entirely aqueous layer-by-layer process. We demonstrate further that the conjugation of R 9 to RNase A permits the assembly of multilayered films under conditions that do not allow for the incorporation of the unmodified protein. This result suggests that R 9 functions as a cationic anchor and serves to increase the strength of electrostatic interactions with SPS and facilitate layer-by-layer assembly. We also demonstrate that RNase A-R 9 /SPS films dissolve rapidly in physiologically relevant media and that macroscopic objects coated with these materials can be used to mediate high levels of protein transduction in mammalian cells. These results suggest the basis of general methods that could contribute to the design of materials that permit spatial and temporal control over the delivery of therapeutic proteins to cells and tissues.

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“…PLL, PLA [18] and their shorter homologues oligo-arginine [14] and oligo-lysine assist this process according to their abilities of charge shielding and aggregation when binding to negatively charged membranes and/or drug molecules [19]. This effect plays a role in the cellular uptake of viruses [11,12] and oligonucleotides [6].…”

Section: Introductionmentioning

confidence: 99%

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

Reuter

Schwieger

Meister

et al. 2009

Biophysical Chemistry

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. Poly-Llysines and poly-L-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane. Biophysical Chemistry, Elsevier, 2009, 144 (1-2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT

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Internalization of cationic peptides: the road less (or more?) traveled

Cited by 88 publications

References 40 publications

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Membrane interaction of a new synthetic antimicrobial lipopeptide sp-85 with broad spectrum activity

Multilayered Films Fabricated from an Oligoarginine-Conjugated Protein Promote Efficient Surface-Mediated Protein Transduction

Poly-l-lysines and poly-l-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane

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