Rational design and structure–activity relationship studies of quercetin–amino acid hybrids targeting the anti-apoptotic protein Bcl-xL

2017 ◽  
Vol 15 (37) ◽  
pp. 7956-7976 ◽  
Author(s):  
Tahsin F. Kellici ◽  
Maria V. Chatziathanasiadou ◽  
Min-Sung Lee ◽  
Nisar Sayyad ◽  
Elena G. Geromichalou ◽  
...  
Keyword(s):  
Amino Acid ◽  
Drug Target ◽  
Rational Design ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Cancer Drug ◽  
Structure Activity ◽  
Apoptotic Protein ◽  
Apoptotic Proteins

Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target.

scholarly journals Structure–Activity Relationship of RGD-Containing Cyclic Octapeptide and αvβ3 Integrin Allows for Rapid Identification of a New Peptide Antagonist

2020 ◽  
Vol 21 (9) ◽  
pp. 3076 ◽  
Author(s):  
Aaron Silva ◽  
Wenwu Xiao ◽  
Yan Wang ◽  
Wei Wang ◽  
Heng Wei Chang ◽  
...  
Keyword(s):  
Rational Design ◽  
Tumor Imaging ◽  
Screening Method ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Sequence Motif ◽  
Αvβ3 Integrin ◽  
Structure Activity ◽  
Cyclic Octapeptide

The αvβ3 integrin, a receptor for many extracellular matrix proteins with RGD-sequence motif, is involved in multiple physiological processes and highly expressed in tumor cells, therefore making it a target for cancer therapy and tumor imaging. Several RGD-containing cyclic octapeptide (named LXW analogs) were screened as αvβ3 antagonists with dramatically different binding affinity, and their structure–activity relationship (SAR) remains elusive. We performed systematic SAR studies and optimized LXW analogs to improve antagonistic potency. The NMR structure of LXW64 was determined and docked to the integrin. Structural comparison and docking studies suggested that the hydrophobicity and aromaticity of the X7 amino acid are highly important for LXW analogs binding to the integrin, a potential hydrophobic pocket on the integrin surface was proposed to play a role in stabilizing the peptide binding. To develop a cost-efficient and fast screening method, computational docking was performed on LXW analogs and compared with in vitro screening. A consistency within the results of both methods was found, leading to the continuous optimization and testing of LXW mutants via in silico screening. Several new LXW analogs were predicted as the integrin antagonists, one of which—LXZ2—was validated by in vitro examination. Our study provides new insight into the RGD recognition specificity and valuable clues for rational design of novel αvβ3 antagonists.

scholarly journals Rational Design, Structure–Activity Relationship, and Immunogenicity of Hypoallergenic Pru p 3 Variants

2019 ◽  
Vol 63 (18) ◽  
pp. 1900336 ◽  
Author(s):  
Stephanie Eichhorn ◽  
Angelika Hörschläger ◽  
Markus Steiner ◽  
Josef Laimer ◽  
Bettina M Jensen ◽  
...  
Keyword(s):  
Rational Design ◽  
Structure Activity Relationship ◽  
Activity Relationship ◽  
Structure Activity ◽  
Design Structure ◽  
Pru P 3
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