scholarly journals Suprastapled Peptides: Hybridization-Enhanced Peptide Ligation and Enforced α-Helical Conformation for Affinity Selection of Combinatorial Libraries

Author(s):  
Pramod M. Sabale ◽  
Mateusz Imiołek ◽  
Pierre Raia ◽  
Sofia Barluenga ◽  
Nicolas Winssinger
1972 ◽  
Vol 136 (2) ◽  
pp. 353-368 ◽  
Author(s):  
Alberto J. L. Macario ◽  
Everly Conway de Macario ◽  
Claudio Franceschi ◽  
Franco Celada

We have cultivated lymph node microfragments from ß-D-galactosidase (Escherichia coli) primed rabbits and have measured their secondary response directed towards the whole molecule (precipitating antibodies) and to a single determinant (activating antibodies) of the antigen. By decreasing the size of the fragments to 105 cells, we began to observe heterogeneity among identical cultures in terms of positivity of response, antibody specificity, and titers. The affinity of "early" activating antibodies was inversely proportional to the dose of challenge. While no maturation was seen in low and excessive challenge, in all cultures receiving intermediate doses the association constant was raised several orders of magnitude within periods of 20 days. The relevance of these data to the mechanism of affinity selection of antigen-sensitive cells is discussed.


2015 ◽  
Vol 11 ◽  
pp. 76-82 ◽  
Author(s):  
John P O’Rourke ◽  
David S Peabody ◽  
Bryce Chackerian

1997 ◽  
Vol 67 (3) ◽  
pp. 199-214 ◽  
Author(s):  
Sean Merlin ◽  
Edwin Rowold ◽  
Ann Abegg ◽  
Cathleen Berglund ◽  
Jon Klover ◽  
...  

1997 ◽  
Vol 10 (5) ◽  
pp. 607-614 ◽  
Author(s):  
F. Martin ◽  
C. Volpari ◽  
C. Steinkuhler ◽  
N. Dimasi ◽  
M. Brunetti ◽  
...  

2008 ◽  
Vol 16 (22) ◽  
pp. 9837-9846 ◽  
Author(s):  
Yoichi Takakusagi ◽  
Kouji Kuramochi ◽  
Manami Takagi ◽  
Tomoe Kusayanagi ◽  
Daisuke Manita ◽  
...  

2016 ◽  
Vol 2 (10) ◽  
pp. e1501695 ◽  
Author(s):  
Ivan V. Smirnov ◽  
Andrey V. Golovin ◽  
Spyros D. Chatziefthimiou ◽  
Anastasiya V. Stepanova ◽  
Yingjie Peng ◽  
...  

In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents. Virtual screening of 167,538 robotically generated mutants identified an optimum single point mutation, which experimentally boosted wild-type Ig scavenger performance by 170-fold. We validated the QM/MM predictions via kinetic analysis and crystal structures of mutant apo-A17 and covalently modified Ig, thereby identifying the displacement of one water molecule by an arginine as delivering this catalysis.


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