Uncoupling the Folding-Function Paradigm of Lytic Peptides to Deliver Impermeable Inhibitors of Intracellular Protein–Protein Interactions

2020 ◽  
Vol 142 (47) ◽  
pp. 19950-19955
Author(s):  
Stephen E. Miller ◽  
Kohei Tsuji ◽  
Rachel P.M. Abrams ◽  
Terrence R. Burke ◽  
Joel P. Schneider
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Lytic Peptides

Assessing the cellular toxicity of peptide inhibitors of intracellular protein-protein interactions by microinjection

2021 ◽  
Vol 29 ◽  
pp. 115906
Author(s):  
Sanjeevini Babu Reddiar ◽  
Hareth Al-Wassiti ◽  
Colin W. Pouton ◽  
Cameron J. Nowell ◽  
Macgregor A. Matthews ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Peptide Inhibitors ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Cellular Toxicity

A Cyclized Helix-Loop-Helix Peptide as a Molecular Scaffold for the Design of Inhibitors of Intracellular Protein-Protein Interactions by Epitope and Arginine Grafting

2016 ◽  
Vol 128 (36) ◽  
pp. 10770-10773 ◽  
Author(s):  
Daisuke Fujiwara ◽  
Hidekazu Kitada ◽  
Masahiro Oguri ◽  
Toshio Nishihara ◽  
Masataka Michigami ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Molecular Scaffold ◽  
Helix Loop Helix

scholarly journals Discovery of cell active macrocyclic peptides with on-target inhibition of KRAS signaling

2021 ◽  
Author(s):  
Shuhui Lim ◽  
Nicolas Boyer ◽  
Nicole Boo ◽  
Chunhui Huang ◽  
Gireedhar Venkatachalam ◽  
...  
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
Therapeutic Targets ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Macrocyclic Peptides

Macrocyclic peptides have the potential to address intracellular protein-protein interactions (PPIs) of high value therapeutic targets that have proven largely intractable to small molecules. Here, we report broadly applicable lessons...

scholarly journals Important Considerations Related to Permeability of Peptides

2021 ◽  
Vol 75 (6) ◽  
pp. 522-524
Author(s):  
Thomas E. Vorherr
Keyword(s):  
Protein Interactions ◽  
Oral Bioavailability ◽  
Intracellular Delivery ◽  
Oral Route ◽  
Assay Development ◽  
Alternative Methods ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
To Come ◽  
Peptide Uptake

This review on intracellular delivery and oral bioavailability of peptides reflects a number of principal investigations at Novartis. Our studies were aimed at either understanding features enabling peptides to interfere with intracellular protein–protein interactions, or to achieve a more patient-friendly delivery by the oral route. In the light of these objectives, we have also spent some effort on assay development to come up with alternative methods for monitoring cellular peptide uptake. This summary of our insights is intended to help in the assessment and development of peptide therapeutics requiring membrane transition

scholarly journals Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability

2020 ◽  
Vol 11 (21) ◽  
pp. 5577-5591 ◽  
Author(s):  
Srinivasaraghavan Kannan ◽  
Pietro G. A. Aronica ◽  
Simon Ng ◽  
Dawn Thean Gek Lian ◽  
Yuri Frosi ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Helical Peptide ◽  
Cellular Permeability ◽  
Targeted Inhibitors

Peptide-based molecules hold great potential as targeted inhibitors of intracellular protein–protein interactions (PPIs).

scholarly journals Macrocycles as protein–protein interaction inhibitors

2017 ◽  
Vol 474 (7) ◽  
pp. 1109-1125 ◽  
Author(s):  
Patrick G. Dougherty ◽  
Ziqing Qian ◽  
Dehua Pei
Keyword(s):  
Small Molecules ◽  
Protein Interactions ◽  
Cyclic Peptides ◽  
Macrocyclic Compounds ◽  
Protein Protein Interactions ◽  
Intracellular Protein ◽  
Drug Candidates ◽  
Protein Protein Interaction ◽  
The Past ◽  
Conventional Drug

Macrocyclic compounds such as cyclic peptides have emerged as a new and exciting class of drug candidates for inhibition of intracellular protein–protein interactions, which are challenging targets for conventional drug modalities (i.e. small molecules and proteins). Over the past decade, several complementary technologies have been developed to synthesize macrocycle libraries and screen them for binding to therapeutically relevant targets. Two different approaches have also been explored to increase the membrane permeability of cyclic peptides. In this review, we discuss these methods and their applications in the discovery of macrocyclic compounds against protein–protein interactions.

Sign in / Sign up

Export Citation Format

Share Document