Binding Characterization of Cyclic Peptide Ligands to Target Proteins and Chemical Epitopes Using ELISA and Fluorescence Polarization Assays

Macrocycle peptides are promising constructs for imaging and inhibiting extracellular, and cell membrane proteins, but their use for targeting intracellular proteins is typically limited by poor cell penetration. We report the development of a cell-penetrant high-affinity peptide ligand targeted to the phosphorylated Ser474 epitope of the (active) Akt2 kinase. This peptide can function as an allosteric inhibitor, an immunoprecipitation reagent, and a live cell immunohistochemical staining reagent. Two cell penetrant stereoisomers were prepared and shown to exhibit similar target binding affinities and hydrophobic character but 2-3-fold different rates of cell penetration. Experimental and computational studies resolved that the ligands’ difference in cell penetration could be assigned to their differential interactions with cholesterol in the membrane. These results expand the tool kit for designing new chiral-based cell-penetrant ligands.

show abstract

Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions

Nag

Mafi

Das

et al. 2023

Commun Chem

View full text Add to dashboard Cite

show abstract

Human cytomegalovirus autophagy is related to the interferon synthesis and mTOR signal pathway

GAO¹,

CHEN²,

LI³

et al. 2022

Biocell

View full text Add to dashboard Cite

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Binding Characterization of Cyclic Peptide Ligands to Target Proteins and Chemical Epitopes Using ELISA and Fluorescence Polarization Assays

Cited by 2 publications

References 21 publications

Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions

Stereochemical engineering yields a multifunctional peptide macrocycle inhibitor of Akt2 by fine-tuning macrocycle-cell membrane interactions

Human cytomegalovirus autophagy is related to the interferon synthesis and mTOR signal pathway

Contact Info

Product

Resources

About