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

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

scholarly journals Divisome under Construction: Distinct Domains of the Small Membrane Protein FtsB Are Necessary for Interaction with Multiple Cell Division Proteins

2009 ◽  
Vol 191 (8) ◽  
pp. 2815-2825 ◽  
Author(s):  
Mark D. Gonzalez ◽  
Jon Beckwith
Keyword(s):  
Cell Division ◽  
Membrane Proteins ◽  
Protein Interactions ◽  
Cell Envelope ◽  
Coiled Coil ◽  
Main Function ◽  
Protein Protein Interactions ◽  
Molecular Scaffold ◽  
C Terminus ◽  
Under Construction

ABSTRACT Cell division in bacteria requires the coordinated action of a set of proteins, the divisome, for proper constriction of the cell envelope. Multiple protein-protein interactions are required for assembly of a stable divisome. Within the Escherichia coli divisome is a conserved subcomplex of inner membrane proteins, the FtsB/FtsL/FtsQ complex, which is necessary for linking the upstream division proteins, which are predominantly cytoplasmic, with the downstream division proteins, which are predominantly periplasmic. FtsB and FtsL are small bitopic membrane proteins with predicted coiled-coil motifs, which themselves form a stable subcomplex that can recruit downstream division proteins independently of FtsQ; however, the details of how FtsB and FtsL interact together and with other proteins remain to be characterized. Despite the small size of FtsB, we identified separate interaction domains of FtsB that are required for interaction with FtsL and FtsQ. The N-terminal half of FtsB is necessary for interaction with FtsL and sufficient, when in complex with FtsL, for recruitment of downstream division proteins, while a portion of the FtsB C terminus is necessary for interaction with FtsQ. These properties of FtsB support the proposal that its main function is as part of a molecular scaffold to allow for proper formation of the divisome.

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

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

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