Peptides, Proteins and Their Derivatives with Therapeutic Applications

A topical collection in Biomolecules (ISSN 2218-273X). This collection belongs to the section "Chemical Biology".

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Editor

Topical Collection Information

Dear Colleagues,

Peptides and proteins are biomolecules known from decades to be important players in physiological and pathological states of all living organisms. This explains why therapeutics based on those molecules were successfully developed in the past and why new therapeutics based on them will emerged.

Furthermore, as therapeutics drugs, in addition to natural peptides and proteins created by Nature, humans created derivatives of them (such as peptidomimetics) that are bioinspired molecules designed in order to mimic the biological activities of peptides/proteins and to correct their limitations including their poor bioavailability, immunogenicity, and/or sensitivity to degradation by proteases.

Peptides/proteins and their derivatives can possess a large panel of biological activities useful to treat humans, animals, or plants diseases making them drug candidates.

As an example, numerous peptides/proteins and their derivatives have been demonstrated to possess anti-infective activity linked to their ability to: i) prevent pathogen’s adhesion to host cells, and/or to ii) directly kill micro-organisms through antimicrobial activity (antibacterial, antiviral, antifungal, or antiparasitic action).

Similarly, peptides/proteins and their derivatives could inhibit the growth and/or cause the death of malignant cells, making them interesting tools to treat cancer.

Many other biological activities have been reported for peptides/proteins and their derivatives including modulatory action of the immune, nerve or endocrine system and/or modifications of cell functions in connection to health or disease.

The topic collection “Peptides, proteins and their derivatives with therapeutic applications” welcomes submissions (reviews and original articles) dealing with all biological activities of natural peptides/proteins and their bio-inspired derivatives, such as peptidomimetics in relation to their potential uses as therapeutics.

Dr. Marc Maresca
Collection Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bio-active peptides/proteins
  • peptidomimetics
  • therapeutic peptides/proteins
  • antimicrobial
  • anticancer
  • antimicrobial peptides
  • anti-inflammatory

Published Papers (2 papers)

2023

12 pages, 1473 KiB  
Article
Development of an Anti-HER2 Single-Chain Variable Antibody Fragment Construct for High-Yield Soluble Expression in Escherichia coli and One-Step Chromatographic Purification
by Kyu Tae Byun, Boram Kim, Junmin Cho, Inbeom Lee, Myung Gu Lee, Dongsun Park, Tae-Bong Kang, Hyung-Sik Won and Chan Gil Kim
Biomolecules 2023, 13(10), 1508; https://doi.org/10.3390/biom13101508 - 11 Oct 2023
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Abstract
Although single-chain variable fragment (scFv) is recognized as a highly versatile scaffold of recombinant antibody fragment molecules, its overexpression in Escherichia coli often leads to the formation of inclusion bodies. To address this issue, we devised and tested four different constructs, named v21, [...] Read more.
Although single-chain variable fragment (scFv) is recognized as a highly versatile scaffold of recombinant antibody fragment molecules, its overexpression in Escherichia coli often leads to the formation of inclusion bodies. To address this issue, we devised and tested four different constructs, named v21, v22, v23 and v24, for producing anti-human epidermal growth factor receptor 2 (HER2) scFv. Among them, the v24 construct obtained from N-terminal fusion of maltose-binding protein (MBP) and subsequent tobacco etch virus protease (TEV) was identified as the most efficient construct for the production of anti-HER2 scFv. Aided by an MBP tag, high-yield soluble expression was ensured and soluble scFv was liberated in cells via autonomous proteolytic cleavage by endogenously expressed TEV. The isolated scFv containing a C-terminal hexahistidine tag was purified through a one-step purification via nickel-affinity chromatography. The purified scFv exhibited a strong (nanomolar Kd) affinity to HER2 both in vitro and in cells. Structural and functional stabilities of the scFv during storage for more than one month were also assured. Given the great utility of anti-HER2 scFv as a basic platform for developing therapeutic and diagnostic agents for cancers, the v24 construct and methods presented in this study are expected to provide a better manufacturing system for producing anti-HER2 scFv with various industrial applications. Full article
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Graphical abstract

14 pages, 1992 KiB  
Article
Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro
by Rika Ishikawa, Kosuke Saito, Takashi Misawa, Yosuke Demizu and Yoshiro Saito
Biomolecules 2023, 13(6), 1002; https://doi.org/10.3390/biom13061002 - 16 Jun 2023
Viewed by 1391
Abstract
ATSP-7041, a stapled α-helical peptide that inhibits murine double minute-2 (MDM2) and MDMX activities, is a promising modality targeting protein–protein interactions. As peptides of molecular weights over 1000 Da are not usually evaluated, data on the drug–drug interaction (DDI) potential of stapled α-helical [...] Read more.
ATSP-7041, a stapled α-helical peptide that inhibits murine double minute-2 (MDM2) and MDMX activities, is a promising modality targeting protein–protein interactions. As peptides of molecular weights over 1000 Da are not usually evaluated, data on the drug–drug interaction (DDI) potential of stapled α-helical peptides remain scarce. Here, we evaluate the interaction of ATSP-7041 with hepatic cytochrome P450s (CYPs; CYP1A2, CYP2C9, CYP2C19, CYP3A4, and CYP2D6) and transporters (organic anion transporting polypeptides (OATPs; OATP1B1 and OATP1B3), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)). ATSP-7041 demonstrated negligible metabolism in human liver S9 fraction and a limited inhibition of CYP activities in yeast microsomes or S9 fractions. On the contrary, a substantial uptake by OATPs in HEK 293 cells, a strong inhibition of OATP activities in the cells, and an inhibition of P-gp and BCRP activities in reversed membrane vesicles were observed for ATSP-7041. A recent report describes that ALRN-6924, an ATSP-7041 analog, inhibited OATP activities in vivo; therefore, we focused on the interaction between ATSP-7041 and OATP1B1 to demonstrate that ATSP-7041, as a higher molecular weight stapled peptide, is a substrate and strong inhibitor of OATP1B1 activity. Our findings demonstrated the possibility of transporter-mediated DDI potential by high molecular weight stapled peptides and the necessity of their evaluation for drug development. Full article
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