Effects of Weak Nonspecific Interactions with ATP on Proteins

Author(s):  
Mayu Nishizawa ◽  
Erik Walinda ◽  
Daichi Morimoto ◽  
Benjamin Kohn ◽  
Ulrich Scheler ◽  
...  
2009 ◽  
Vol 53 (4) ◽  
pp. 1528-1531 ◽  
Author(s):  
Françoise Banères-Roquet ◽  
Maxime Gualtieri ◽  
Philippe Villain-Guillot ◽  
Martine Pugnière ◽  
Jean-Paul Leonetti

ABSTRACT The pharmacologic effect of an antibiotic is directly related to its unbound concentration at the site of infection. Most commercial antibiotics have been selected in part for their low propensity to interact with serum proteins. These nonspecific interactions are classically evaluated by measuring the MIC in the presence of serum. As higher-throughput technologies tend to lose information, surface plasmon resonance (SPR) is emerging as an informative medium-throughput technology for hit validation. Here we show that SPR is a useful automatic tool for quantification of the interaction of model antibiotics with serum proteins and that it delivers precise real-time kinetic data on this critical parameter.


2019 ◽  
Vol 62 (10) ◽  
pp. 5063-5079 ◽  
Author(s):  
Stephen Boulton ◽  
Rajeevan Selvaratnam ◽  
Rashik Ahmed ◽  
Katherine Van ◽  
Xiaodong Cheng ◽  
...  

2020 ◽  
Vol 30 (28) ◽  
pp. 2070187
Author(s):  
Martina Giordani ◽  
Matteo Sensi ◽  
Marcello Berto ◽  
Michele Di Lauro ◽  
Carlo Augusto Bortolotti ◽  
...  

2003 ◽  
Vol 2003 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Andreas G. Schätzlein

Safe, efficient, and specific delivery of therapeutic genes remains an important bottleneck for the development of gene therapy. Synthetic, nonviral systems have a unique pharmaceutical profile with potential advantages for certain applications. Targeting of the synthetic vector improves the specificity of gene medicines through a modulation of the carriers' biodistribution, thus creating a dose differential between healthy tissue and the target site. The biodistribution of current carrier systems is being influenced to a large extent by intrinsic physicochemical characteristics, such as charge and size. Consequently, such nonspecific interactions can interfere with specific targeting, for example, by ligands. Therefore, a carrier complex should ideally be inert, that is, free from intrinsic properties that would bias its distribution away from the target site. Strategies such as coating of DNA carrier complexes with hydrophilic polymers have been used to mask some of these intrinsic targeting effects and avoid nonspecific interactions. Preexisting endogenous ligand-receptor interactions have frequently been used for targeting to certain cell types or tumours. Recently exogenous ligands have been derived from microorganisms or, like antibodies or phage-derived peptides, developed de novo. In animal models, such synthetic vectors have targeted remote sites such as a tumour. Furthermore, the therapeutic proof of the concept has been demonstrated for fitting combinations of synthetic vectors and therapeutic gene.


2011 ◽  
Vol 286 (22) ◽  
pp. 19470-19477 ◽  
Author(s):  
Maryna Gorelik ◽  
Karen Stanger ◽  
Alan R. Davidson

The yeast Bem1p SH3b and Nbp2p SH3 domains are unusual because they bind to peptides containing the same consensus sequence, yet they perform different functions and display low sequence similarity. In this work, by analyzing the interactions of these domains with six biologically relevant peptides containing the consensus sequence, they are shown to possess finely tuned and distinct binding specificities. We also identify a residue in the Bem1p SH3b domain that inhibits binding, yet is highly conserved for the purpose of preventing nonspecific interactions. Substitution of this residue results in a marked reduction of in vivo function that is caused by titration of the domain away from its proper targets through nonspecific interactions with other proteins. This work provides a clear illustration of the importance of intrinsic binding specificity for the function of protein-protein interaction modules, and the key role of “negative” interactions in determining the specificity of a domain.


2012 ◽  
Vol 3 (12) ◽  
pp. 3488 ◽  
Author(s):  
Andrew D. White ◽  
Ann K. Nowinski ◽  
Wenjun Huang ◽  
Andrew J. Keefe ◽  
Fang Sun ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document