scholarly journals A preorganized β-amino acid bearing a guanidinium side chain and its use in cell-penetrating peptides

2015 ◽  
Vol 13 (20) ◽  
pp. 5617-5620 ◽  
Author(s):  
Yosuke Demizu ◽  
Makoto Oba ◽  
Koyo Okitsu ◽  
Hiroko Yamashita ◽  
Takashi Misawa ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Penetrating Peptides ◽  
Side Chain ◽  
Cell Penetrating ◽  
Guanidinium Group

A cyclic β-amino acid (APCGu) bearing a side-chain guanidinium group has been developed.

A Novel Amino Acid Sequence-based Computational Approach to Predicting Cell-penetrating Peptides

2019 ◽  
Vol 15 (3) ◽  
pp. 206-211 ◽  
Author(s):  
Jihui Tang ◽  
Jie Ning ◽  
Xiaoyan Liu ◽  
Baoming Wu ◽  
Rongfeng Hu
Keyword(s):  
Machine Learning ◽  
Amino Acid ◽  
Amino Acid Position ◽  
Cell Penetrating Peptides ◽  
Support Vector ◽  
Cell Penetration ◽  
Drug Candidates ◽  
Machine Learning Model ◽  
Cell Penetrating ◽  
Novel Method

<P>Introduction: Machine Learning is a useful tool for the prediction of cell-penetration compounds as drug candidates. </P><P> Materials and Methods: In this study, we developed a novel method for predicting Cell-Penetrating Peptides (CPPs) membrane penetrating capability. For this, we used orthogonal encoding to encode amino acid and each amino acid position as one variable. Then a software of IBM spss modeler and a dataset including 533 CPPs, were used for model screening. </P><P> Results: The results indicated that the machine learning model of Support Vector Machine (SVM) was suitable for predicting membrane penetrating capability. For improvement, the three CPPs with the most longer lengths were used to predict CPPs. The penetration capability can be predicted with an accuracy of close to 95%. </P><P> Conclusion: All the results indicated that by using amino acid position as a variable can be a perspective method for predicting CPPs membrane penetrating capability.</P>

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

Cyclic, Cell-Penetrating Peptides Tailor-Made for the Creation of Peptide Libraries with Intrinsic Cell Permeability

2020 ◽  
Author(s):  
Nicolas A. Abrigo ◽  
Kara Dods ◽  
Koushambi Mitra ◽  
Kaylee Newcomb ◽  
Anthony Le ◽  
...  
Keyword(s):  
Cyclic Peptide ◽  
Cell Penetrating Peptides ◽  
Peptide Libraries ◽  
Cell Permeability ◽  
Side Chain ◽  
High Affinity ◽  
Cell Penetrating ◽  
The Creation ◽  
Intracellular Targets ◽  
Macrocyclic Peptide

<p>The discovery of high-affinity peptides to many intracellular targets has become feasible through the development of diverse macrocyclic peptide libraries. But lack of cell permeability is a key feature hampering the use of these peptides as therapeutics. Here, we develop a set of small, cyclic peptide carriers that efficiently carry cargoes into the cytosol. These peptides are cyclized via side-chain alkylation, which makes them ideal for the creation of diverse mRNA or phage-displayed libraries with intrinsic cell permeability.</p>

scholarly journals Novel Lung Targeting Cell Penetrating Peptides as Vectors for Delivery of Therapeutics

2021 ◽  
Author(s):  
Maliha Zahid ◽  
Kayla McCandless ◽  
Sanjay Mishra ◽  
Jeffrey Stiltner ◽  
Kyle Feldman ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lung Tissue ◽  
Cell Penetrating Peptides ◽  
Mouse Lung ◽  
Specific Cell ◽  
Lung Targeting ◽  
Biodistribution Studies ◽  
Cell Penetrating

Abstract Cell penetrating peptides are unique, 5-30 amino acid long peptides that are able to breach cell membrane barriers and carry cargoes intracellularly in a functional form. Our prior work identified a synthetic, non-naturally occurring 12-amino acid long peptide that we termed cardiac targeting peptide (CTP: APWHLSSQYSRT) due to its ability to transduce cardiomyocytes in vivo. Studies looking into its mechanism of transduction identified two lung targeting peptides (LTPs), S7A (APWHLSAQYSRT) and R11A (APWHLSSQYSAT). These peptides robustly transduced human bronchial epithelial cell lines in vitro and mouse lung tissue in vivo. This uptake occurred independently of clathrin mediated endocytosis. Biodistribution studies of R11A showed peak uptake at 15 minutes with uptake in liver but not kidneys, indicating primarily a hepatobiliary mode of excretion. Cyclic version of both peptides was ~100-fold more efficient in permeating cells than their linear counterparts. As proof of principle, we conjugated anti-spike and anti-envelope SARS-CoV-2 siRNAs to cyclized R11A and demonstrate anti-viral efficacy in vitro. Our work presented here identifies two novel lung-specific cell penetrating peptides that could potentially deliver myriad therapeutic cargoes to lung tissue.

Enzyme-Activatable Cell-Penetrating Peptides through a Minimal Side Chain Modification

2015 ◽  
Vol 26 (5) ◽  
pp. 850-856 ◽  
Author(s):  
Saskia A. Bode ◽  
Morten B. Hansen ◽  
Roy A. J. F. Oerlemans ◽  
Jan C. M. van Hest ◽  
Dennis W. P. M. Löwik
Keyword(s):  
Cell Penetrating Peptides ◽  
Side Chain ◽  
Cell Penetrating

scholarly journals Peptide Stapling Improves the Sustainability of a Peptide-Based Chimeric Molecule That Induces Targeted Protein Degradation

2021 ◽  
Vol 22 (16) ◽  
pp. 8772
Author(s):  
Hidetomo Yokoo ◽  
Nobumichi Ohoka ◽  
Mami Takyo ◽  
Takahito Ito ◽  
Keisuke Tsuchiya ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Estrogen Receptor Alpha ◽  
Cell Penetrating Peptides ◽  
Side Chain ◽  
Binding Peptide ◽  
Stapled Peptide ◽  
Chimeric Peptide ◽  
Cell Penetrating ◽  
Natural Amino Acids ◽  
Peptide Stapling

Peptide-based target protein degradation inducers called PROTACs/SNIPERs have low cell penetrability and poor intracellular stability as drawbacks. These shortcomings can be overcome by easily modifying these peptides by conjugation with cell penetrating peptides and side-chain stapling. In this study, we succeeded in developing the stapled peptide stPERML-R7, which is based on the estrogen receptor alpha (ERα)-binding peptide PERML and composed of natural amino acids. stPERML-R7, which includes a hepta-arginine motif and a hydrocarbon stapling moiety, showed increased α-helicity and similar binding affinity toward ERα when compared with those of the parent peptide PERML. Furthermore, we used stPERML-R7 to develop a peptide-based degrader LCL-stPERML-R7 targeting ERα by conjugating stPERML-R7 with a small molecule LCL161 (LCL) that recruits the E3 ligase IAPs to induce proteasomal degradation via ubiquitylation. The chimeric peptide LCL-stPERML-R7 induced sustained degradation of ERα and potently inhibited ERα-mediated transcription more effectively than the unstapled chimera LCL-PERML-R7. These results suggest that a stapled structure is effective in maintaining the intracellular activity of peptide-based degraders.

scholarly journals Cell-penetrating peptides as transporters for morpholino oligomers: effects of amino acid composition on intracellular delivery and cytotoxicity

2007 ◽  
Vol 35 (15) ◽  
pp. 5182-5191 ◽  
Author(s):  
R. P. Wu ◽  
D. S. Youngblood ◽  
J. N. Hassinger ◽  
C. E. Lovejoy ◽  
M. H. Nelson ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Cell Penetrating

Peptide-based delivery of nucleic acids: design, mechanism of uptake and applications to splice-correcting oligonucleotides

2007 ◽  
Vol 35 (1) ◽  
pp. 53-55 ◽  
Author(s):  
S. Abes ◽  
H. Moulton ◽  
J. Turner ◽  
P. Clair ◽  
J.P. Richard ◽  
...  
Keyword(s):  
Amino Acid ◽  
Cell Membrane ◽  
Cell Surface ◽  
Nucleic Acids ◽  
Peptide Nucleic Acids ◽  
Basic Amino Acid ◽  
Cell Penetrating Peptides ◽  
Cellular Delivery ◽  
Cell Penetrating ◽  
Design Mechanism

CPPs (cell-penetrating peptides) have given rise to much interest for the delivery of biomolecules such as peptides, proteins or ONs (oligonucleotides). CPPs and their conjugates were initially thought to translocate through the cell membrane by a non-endocytotic mechanism which has recently been re-evaluated. Basic-amino-acid-rich CPPs first interact with cell-surface proteoglycans before being internalized by endocytosis. Sequestration and degradation in endocytotic vesicles severely limits the cytoplasmic and nuclear delivery of the conjugated biomolecules. Accordingly, splicing correction by CPP-conjugated steric-block ON analogues is inefficient in the absence of endosomolytic agents. New arginine-rich CPPs allowing efficient splicing correction by conjugated PNAs (peptide nucleic acids) or PMO (phosphorodiamidate morpholino oligomer) steric blockers in the absence of endosomolytic agents have recently been defined in our group and are currently being characterized. They offer promising leads for the development of efficient cellular delivery vectors for therapeutic steric-block ON analogues.

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