scholarly journals Protease-Resistant Peptides for Targeting and Intracellular Delivery of Therapeutics

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2065
Author(s):  
Maria C. Lucana ◽  
Yolanda Arruga ◽  
Emilia Petrachi ◽  
Albert Roig ◽  
Roberta Lucchi ◽  
...  
Keyword(s):  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Peptide Transport ◽  
Transport Capacity ◽  
Cell Penetration ◽  
Transport Efficiency ◽  
Degree Of Protection ◽  
Protease Resistance ◽  
Backbone Modification ◽  
The Brain

Peptides show high promise in the targeting and intracellular delivery of next-generation bio- and nano-therapeutics. However, the proteolytic susceptibility of peptides is one of the major limitations of their activity in biological environments. Numerous strategies have been devised to chemically enhance the resistance of peptides to proteolysis, ranging from N- and C-termini protection to cyclization, and including backbone modification, incorporation of amino acids with non-canonical side chains and conjugation. Since conjugation of nanocarriers or other cargoes to peptides for targeting and cell penetration may already provide some degree of shielding, the question arises about the relevance of using protease-resistant sequences for these applications. Aiming to answer this question, here we provide a critical review on protease-resistant targeting peptides and cell-penetrating peptides (CPPs). Two main approaches have been used on these classes of peptides: enantio/retro-enantio isomerization and cyclization. On one hand, enantio/retro-enantio isomerization has been shown to provide a clear enhancement in peptide efficiency with respect to parent L-amino acid peptides, especially when applied to peptides for drug delivery to the brain. On the other hand, cyclization also clearly increases peptide transport capacity, although contribution from enhanced protease resistance or affinity is often not dissected. Overall, we conclude that although conjugation often offers some degree of protection to proteolysis in targeting peptides and CPPs, modification of peptide sequences to further enhance protease resistance can greatly increase homing and transport efficiency.

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>

Root water gates and not changes in root structure provide new insights into plant physiological responses to drought, flooding and salinity

2021 ◽  
Author(s):  
Jean-Christophe Domec ◽  
John S King ◽  
Mary J Carmichael ◽  
Anna Treado Overby ◽  
Remi R Wortemann ◽  
...  
Keyword(s):  
Pinus Taeda ◽  
Vapor Pressure Deficit ◽  
Water Movement ◽  
Root Structure ◽  
Transport Capacity ◽  
Transport Efficiency ◽  
Xylem Structure ◽  
Plant Hydraulics ◽  
Whole Plant ◽  
The Impact

Abstract The influence of aquaporin (AQP) activity on plant water movement remains unclear, especially in plants subject to unfavorable conditions. We applied a multitiered approach at a range of plant scales to (i) characterize the resistances controlling water transport under drought, flooding and flooding plus salinity conditions; (ii) quantify the respective effects of AQP activity and xylem structure on root (Kroot), stem (Kstem) and leaf (Kleaf) conductances, and (iii) evaluate the impact of AQP-regulated transport capacity on gas exchange. We found that drought, flooding and flooding-salinity reduced Kroot and root AQP activity in Pinus taeda, whereas Kroot of the flood-tolerant Taxodium distichum did not decline under flooding. The extent of the AQP-control of transport efficiency varied among organs and species, ranging from 35%-55% in Kroot to 10%-30% in Kstem and Kleaf. In response to treatments, AQP-mediated inhibition of Kroot rather than changes in xylem acclimation controlled the fluctuations in Kroot. The reduction in stomatal conductance and its sensitivity to vapor pressure deficit were direct responses to decreased whole-plant conductance triggered by lower Kroot and larger resistance belowground. Our results provide new mechanistic and functional insights on plant hydraulics that are essential to quantifying the influences of future stress on ecosystem function.

scholarly journals Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules

2005 ◽  
Vol 390 (2) ◽  
pp. 407-418 ◽  
Author(s):  
Catherine de Coupade ◽  
Antonio Fittipaldi ◽  
Vanessa Chagnas ◽  
Matthieu Michel ◽  
Sophie Carlier ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Mammalian Cells ◽  
Heparan Sulphate ◽  
Intracellular Delivery ◽  
Membrane Lipid ◽  
Cell Penetrating Peptides ◽  
Heparin Binding ◽  
Independent Manner ◽  
Cell Penetrating

Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell® peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell® peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell® peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.

Therapeutic delivery using cell-penetrating peptides

2013 ◽  
Vol 5 (3) ◽  
Author(s):  
Rupa R. Sawant ◽  
Niravkumar R. Patel ◽  
Vladimir P. Torchilin
Keyword(s):  
Small Molecules ◽  
Therapeutic Agent ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Current Status ◽  
Unique Challenge ◽  
Large Molecules ◽  
Therapeutic Delivery ◽  
Cell Penetrating ◽  
Stimuli Sensitive

AbstractIntracellular delivery of promising therapeutic agents as well as nanocarriers presents a unique challenge. However, with the discovery of the cell-penetrating peptides (CPPs), overcoming this obstacle seems more plausible. In many cases, CPPs conjugated with therapeutic agent or therapeutic agent loaded-nanoparticles have shown promising results via increased cellular uptake. In this review, the current status of CPPs for the intracellular delivery of not just potential therapeutic small molecules but also large molecules like peptides, nucleic acids and nanocarriers is discussed. In addition, the design of ‘smart stimuli-sensitive nanocarrier’ to overcome the non-target-specificity of CPPs is also described.

Intracellular Delivery of Histidine and Arginine Rich Cell Penetrating Peptides into HeLa cell Line

2015 ◽  
Vol 5 (4) ◽  
pp. 695
Author(s):  
Shikha Saxena ◽  
Deepika Bisht ◽  
Basavaraj Sajjanar ◽  
Arvind Kumar Singh ◽  
Aditya Prasad Sahoo ◽  
...  
Keyword(s):  
Hela Cell ◽  
Cell Line ◽  
Intracellular Delivery ◽  
Cell Penetrating Peptides ◽  
Hela Cell Line ◽  
Cell Penetrating

A Fluorescence-Based High Throughput Screen for the Transporter Associated with Antigen Processing

1999 ◽  
Vol 4 (2) ◽  
pp. 87-91 ◽  
Author(s):  
Jonathan M. Blevitt ◽  
Klaus Fruh ◽  
Charlie Glass ◽  
Michael R. Jackson ◽  
Per A. Peterson ◽  
...  
Keyword(s):  
Antigen Processing ◽  
Time Course ◽  
Peptide Transport ◽  
Fluorescent Label ◽  
Radioactive Label ◽  
Transport Efficiency ◽  
Discovery Research ◽  
Histocompatibility Complex ◽  
Drug Discovery Research ◽  
Similar Kinetic

The transporter associated with antigen processing (TAP) is essential for antigen presentation by major histocompatibility complex (MHC) class I molecules. Traditional methods used to analyze peptide transport mediated by TAP require radioactive labeling of peptides and time-consuming manipulation of Concanavalin A-Sepharose. Drug discovery research requires rapid and reliable evaluation of large number of samples for bioactivity. To meet these requirements a nonradioactive, HTS assay for peptide transport activity of TAP has been developed. The radioactive label in the traditional assays has been replaced by a fluorescent label without compromising the transport efficiency of labeled peptide or the sensitivity of the assay. The use of multiscreen filtration plates has facilitated higher throughput and eliminated the centrifugation steps used in traditional TAP assays. The HTS assay shows similar kinetic characteristics as compared to the traditional assay. The HTS assay has been adapted on a Quadra™ 96-32096-channel pipetting station (Tomtec, Hamden, CT) by optimizing time course, dose response of TAP to peptides and adenosine triphosphate (ATP), signal/noise ratio, reproducibility, and reagent stability. This HTS system has been utilized to screen a multiplexed compound library with a maximum of throughput 17,600 compounds per week.

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