Phage display technology for target determination of small-molecule therapeutics: an update

Takakusagi, Yoichi; Takakusagi, Kaori; Sakaguchi, Kengo; Sugawara, Fumio

doi:10.1080/17460441.2020.1790523

Cited by 14 publications

(5 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are many examples of engineered grafted cyclotides and PDPs in which other epitopes are appended to the cyclic scaffolds, endowing new therapeutical activities 199 . Moreover, the short peptides (3–15 aa) discovered from phage combinatorial libraries have displayed potent activities against inflammation and different types of tumors 200 . However, the in vivo data demonstrated rapid kidney clearance and short half‐lives of these peptides, diminishing drug bioavailability after administration 201 .…”

Section: Discussionmentioning

confidence: 99%

Exploring and exploiting plant cyclic peptides for drug discovery and development

Zhang

Yuan

et al. 2021

Medicinal Research Reviews

View full text Add to dashboard Cite

Ever since the discovery of insulin, natural peptides have become an important resource for therapeutic development. Decades of research has led to the discovery of a long list of peptide drugs with broad applications in clinics, from antibiotics to hypertension treatment to pain management. Many of these US FDA‐approved peptide drugs are derived from microorganisms and animals. By contrast, the great potential of plant cyclic peptides as therapeutics remains largely unexplored. These macrocyclic peptides typically have rigid structures, good bioavailability and membrane permeability, making them appealing candidates for drug development and engineering. In this review, we introduce the three major classes of plant cyclic peptides and summarize their potential medical applications. We discuss how we can leverage the genome information of many different plants to quickly search for new cyclic peptides and how we can take advantage of the insights gained from their biosynthetic pathways to transform the process of production and drug development. These recent developments have provided a new angle for exploring and exploiting plant cyclic peptides, and we believe that many more peptide drugs derived from plants are about to come.

show abstract

Section: Discussionmentioning

confidence: 99%

Exploring and exploiting plant cyclic peptides for drug discovery and development

Zhang

Yuan

et al. 2021

Medicinal Research Reviews

View full text Add to dashboard Cite

show abstract

“…Nevertheless, similarity search or mining of conserved motifs allows the detection of the amino acids comprising the drug-binding sites of proteins even with this limited diversity of peptides in the library. In addition, 3 -5 amino acid stretches within the library peptide (the appearance rate is between 1/20 3 and 1/ 20 5 , which can be realized using the T7 phage display system) are involved in the recognition of small molecule drugs; therefore, a 100% match of the peptide sequences with 15-mer amino acid sequences constituting the drug binding site of the target protein is not required. Indeed, approximately 30 affinityselected peptides successfully highlighted the binding site of the target protein for each drug tested (Figure 4).…”

Section: Discussionmentioning

confidence: 99%

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Takakusagi

2020

JoVE

View full text Add to dashboard Cite

Receptors and enzyme proteins are important biomolecules that act as binding targets for bioactive small molecules. Thus, the rapid and global validation of the drug-protein interactions is highly desirable for not only understanding the molecular mechanisms underlying therapeutic efficacy but also for assessing drug characteristics, such as adsorption, distribution, metabolism, excretion, and toxicity (ADMET) for clinical use.Here, we present a biosensor-based high throughput strategy for the biopanning of T7 phage-displayed short peptides that can be easily displayed on the phage capsid. Subsequent analysis of the amino acid sequences of peptides containing short segments, as "broken relics", of the drug-binding sites using bioinformatics programs in receptor ligand contact (RELIC) suite, is also shown. By applying this method to two clinically approved drugs, an anti-tumor irinotecan, and an anti-flu oseltamivir, the detailed process for collecting the drug-recognizing peptide sequences and highlighting the drug-binding sites of the target proteins are explained in this paper.The strategy described herein can be applied for any small molecules of interest.

show abstract

“…There are other peptides known to block the interaction between CD81 and the E2 protein of the virus [ 144 ]. Small-molecule-oriented phage display methods may be useful to generate anti-CD81 binders, although it is often a difficult process to transform peptides into small molecules without losing activity or selectivity [ 145 ].…”

Section: Regulation Of Cd81 Expression or Functions With Antibodies A...mentioning

confidence: 99%

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Bailly

Thuru

2023

Cancers

View full text Add to dashboard Cite

Tetraspanin CD81 plays major roles in cell-cell interactions and the regulation of cellular trafficking. This cholesterol-embarking transmembrane protein is a co-receptor for several viruses, including HCV, HIV-1 and Chikungunya virus, which exploits the large extracellular loop EC2 for cell entry. CD81 is also an anticancer target implicated in cancer cell proliferation and mobility, and in tumor metastasis. CD81 signaling contributes to the development of solid tumors (notably colorectal, liver and gastric cancers) and has been implicated in the aggressivity of B-cell lymphomas. A variety of protein partners can interact with CD81, either to regulate attachment and uptake of viruses (HCV E2, claudin-1, IFIM1) or to contribute to tumor growth and dissemination (CD19, CD44, EWI-2). CD81-protein interactions can be modulated with molecules targeting the extracellular domain of CD81, investigated as antiviral and/or anticancer agents. Several monoclonal antibodies anti-CD81 have been developed, notably mAb 5A6 active against invasion and metastasis of triple-negative breast cancer cells. CD81-EC2 can also be targeted with natural products (trachelogenin and harzianoic acids A-B) and synthetic compounds (such as benzothiazole-quinoline derivatives). They are weak CD81 binders but offer templates for the design of new compounds targeting the open EC2 loop. There is no anti-CD81 compound in clinical development at present, but this structurally well-characterized tetraspanin warrants more substantial considerations as a drug target.

show abstract

Phage display technology for target determination of small-molecule therapeutics: an update

Cited by 14 publications

References 86 publications

Exploring and exploiting plant cyclic peptides for drug discovery and development

Exploring and exploiting plant cyclic peptides for drug discovery and development

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases

Contact Info

Product

Resources

About