AI Article Synopsis
- Peptide drugs face challenges in cancer therapy due to their low stability and poor ability to penetrate cells, highlighting the need for improved options.
- Researchers discovered a new cyclic d-peptide, NKTP-3, which is biostable and effectively penetrates cells, specifically targeting proteins NRP1 and KRAS.
- NKTP-3 showed promising results by inhibiting growth in cancer cells with KRAS mutations and demonstrated strong antitumor effects in animal models without significant toxicity.
Article Abstract
The application of peptide drugs in cancer therapy is impeded by their poor biostability and weak cell permeability. Therefore, it is imperative to find biostable and cell-permeable peptide drugs for cancer treatment. Here, we identified a potent, selective, biostable, and cell-permeable cyclic d-peptide, NKTP-3, that targets NRP1 and KRAS using structure-based virtual screening. NKTP-3 exhibited strong biostability and cellular uptake ability. Importantly, it significantly inhibited the growth of A427 cells with the KRAS mutation. Moreover, NKTP-3 showed strong antitumor activity against A427 cell-derived xenograft and KRAS-driven primary lung cancer models without obvious toxicity. This study demonstrates that the dual NRP1/KRAS-targeting cyclic d-peptide NKTP-3 may be used as a potential chemotherapeutic agent for KRAS-driven lung cancer treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.1c12075 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Highly Potent, Selective, Biostable, and Cell-Permeable Cyclic d-Peptide for Dual-Targeting Therapy of Lung Cancer.
J Am Chem Soc
April 2022
Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Article Synopsis
- Peptide drugs face challenges in cancer therapy due to their low stability and poor ability to penetrate cells, highlighting the need for improved options.
- Researchers discovered a new cyclic d-peptide, NKTP-3, which is biostable and effectively penetrates cells, specifically targeting proteins NRP1 and KRAS.
- NKTP-3 showed promising results by inhibiting growth in cancer cells with KRAS mutations and demonstrated strong antitumor effects in animal models without significant toxicity.
SialoPen peptides are new cationic foldamers with remarkable cell permeability.
Heliyon
December 2020
Department of Chemistry, Washington State University, Pullman, WA 99164, USA.
The ability to access intracellular targets is of vital importance as the number of identified druggable intracellular targets increases every year. However, intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes, which hinders their practical application in drug development. Herein we present -designed unnatural cell penetrating peptide foldamers utilizing a 2,3-Didehydro-2-deoxyneuraminic acid (Neu2en) scaffold.
View Article and Find Full Text PDFProtease-Resistant and Cell-Permeable Double-Stapled Peptides Targeting the Rab8a GTPase.
ACS Chem Biol
August 2016
Technische Universität Dortmund, Fakultät für Chemie und Chemische Biologie, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany.
Small GTPases comprise a family of highly relevant targets in chemical biology and medicinal chemistry research and have been considered "undruggable" due to the persisting lack of effective synthetic modulators and suitable binding pockets. As molecular switches, small GTPases control a multitude of pivotal cellular functions, and their dysregulation is associated with many human diseases such as various forms of cancer. Rab-GTPases represent the largest subfamily of small GTPases and are master regulators of vesicular transport interacting with various proteins via flat and extensive protein-protein interactions (PPIs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!