Replacement of a Proline with Silaproline Causes a 20-Fold Increase in the Cellular Uptake of a Pro-Rich Peptide

Pujals, Sílvia; Fernández‐Carneado, Jimena; Kogan, Marcelo J.; Martinez, Jean; Cavelier, Florine; Giralt, Ernest

doi:10.1021/ja060036c

Cited by 66 publications

(63 citation statements)

References 26 publications

(31 reference statements)

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“…In another study, cholesterol-derivatized oligonucleotides also showed a rapid binding and cytosolic partition in cells [62]. Closer to the CPP context, cell delivery improvement has been also observed upon stearylation of an octa-arginine peptide [63] or following the introduction of a proline amino acid derivative with a higher hydrophobicity into a prolinerich CPP [64]. In most of these studies, except for the last one, the derivatization of peptides with lipids was performed at the N-terminal end as it allowed easy coupling of the lipid by conventional amide bond formation directly on the peptidyl-resin after completion of the peptide sequence.…”

Section: Cpps and Cell Entrymentioning

confidence: 87%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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During the last decade, the potential of peptides for drug delivery into cells has been highlighted by the discovery of several cell-penetrating peptides (CPPs). CPPs are very efficient in delivering various molecules into cells. However, except in some specific cases, their lack of cell specificity remains the major drawback for their clinical development. At the same time, various peptides with specific binding activity for a given cell line (cell-targeting peptides) have also been reported in the literature. One of the goals of the next years will be to optimize the tissue and cell delivery of therapeutic molecules by means of peptides which combine both targeting and internalization advantages. In this review, we describe the main strategies that are currently in use or likely to be employed in the near future to associate both targeting and delivery properties.

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Section: Cpps and Cell Entrymentioning

confidence: 87%

Cell-penetrating and cell-targeting peptides in drug delivery

Vivès

Schmidt

Pèlegrin

2008

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

315

272

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“…Another promising SAP derivative is one in which a Pro of the hydrophobic face of the peptide is replaced by a Sip (g-(dimethylsila)-proline), providing a 20-fold increase in the cell uptake level. [19] In the present work, we set about answering the following questions: 1) Would an all-d version retain the cell-penetrating ability of SAP? ; and 2) Would an all-d version retain the noncytotoxicity of the original?…”

Section: Introductionmentioning

confidence: 99%

D‐SAP: A New, Noncytotoxic, and Fully Protease Resistant Cell‐Penetrating Peptide

Pujals

Fernández‐Carneado

Ludevid³

et al. 2008

ChemMedChem

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Protease resistant cell-penetrating peptides (CPPs) are promising carriers for drugs unable to cross the cell membrane. As these CPPs are stable in vivo for much longer periods of time compared to other classes of therapeutic peptides, noncytotoxicity is a property sine qua non for their pharmacological development. Described herein is a fully protease resistant CPP that is noncytotoxic at concentrations up to 1 mM. Proteolytic stability was obtained by chiral inversion of the residues of a known self-assembling CPP-from all L-amino acids to all D-amino acids-and then assessed against trypsin and human serum. Circular dichroism studies confirmed the enantiomeric structure of the analogue, and transmission electron microscopy (TEM) studies indicated that the new inverso analogue retains the ability of the original peptide to self-assemble. The results of uptake experiments indicate that the protease-stable (that is, D-amino acid) analogue of the peptide is internalised by cells to the same extent as the protease-susceptible (that is, L-amino acid) parent peptide. Also reported herein are the results of studies on the cellular internalisation mechanism of the all-D analogue, which reveal the steps followed by the peptide upon its entry into the cell.

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“…[9] In ar ecent study,t he a,a-disubstituted disilylated amino acid TESDpgw as synthesizeda nd incorporated into different positions in the antimicrobialp eptidea lamethicin. [10] The study showed that the a-helical structureo fa lamethicin was retained; however,t he antimicrobial activity against B. subtilis was lost for all the peptide analogues, possibly due to steric hindrance from the bulky amino acid preventing self-association of the peptideinthe membrane.…”

Section: Introductionmentioning

confidence: 99%

Incorporation of β‐Silicon‐β3‐Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20‐Fold Increase in Membrane Permeabilization

Madsen

Hjørringgaard

Vad

et al. 2016

Chemistry A European J

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Incorporation of silicon-containing amino acids in peptides is known to endow the peptide with desirable properties such as improved proteolytic stability and increased lipophilicity. In the presented study, we demonstrate that incorporation of β-silicon-β3-amino acids into the antimicrobial peptide alamethicin provides the peptide with improved membrane permeabilizing properties. A robust synthetic procedure for the construction of β-silicon-β3-amino acids was developed and the amino acid analogues were incorporated into alamethicin at different positions of the hydrophobic face of the amphipathic helix by using SPPS. The incorporation was shown to provide up to 20-fold increase in calcein release as compared with wild-type alamethicin.

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Replacement of a Proline with Silaproline Causes a 20-Fold Increase in the Cellular Uptake of a Pro-Rich Peptide

Cited by 66 publications

References 26 publications

Cell-penetrating and cell-targeting peptides in drug delivery

Cell-penetrating and cell-targeting peptides in drug delivery

D‐SAP: A New, Noncytotoxic, and Fully Protease Resistant Cell‐Penetrating Peptide

Incorporation of β‐Silicon‐β3‐Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20‐Fold Increase in Membrane Permeabilization

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