scholarly journals DNA display of fragment pairs as a tool for the discovery of novel biologically active small molecules

2015 ◽  
Vol 6 (1) ◽  
pp. 739-744 ◽  
Author(s):  
J.-P. Daguer ◽  
C. Zambaldo ◽  
M. Ciobanu ◽  
P. Morieux ◽  
S. Barluenga ◽  
...  
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Biologically Active ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

A focused library for Hsp70 was prepared from fragments identified from an array combinatorially pairing two libraries of small molecule fragments. Screening of the focus library yielded high affinity ligand to Hsp70.

scholarly journals Novel Pure αVβ3 Integrin Antagonists That Do Not Induce Receptor Extension, Prime the Receptor, or Enhance Angiogenesis at Low Concentrations

2019 ◽  
Author(s):  
Jihong Li ◽  
Yoshiyuki Fukase ◽  
Yi Shang ◽  
Wei Zou ◽  
José M. Muñoz-Félix ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Conformational Change ◽  
Small Molecule ◽  
High Affinity ◽  
Partial Agonists ◽  
Affinity Ligand ◽  
Human Therapy ◽  
High Affinity Ligand

AbstractThe integrin αVβ3 receptor has been implicated in several important diseases, but no αVβ3 antagonists are approved for human therapy. One possible limitation of current small-molecule antagonists is their ability to induce a major conformational change in the receptor that induces it to adopt a high-affinity ligand-binding state. In response, we used structural inferences from a pure peptide antagonist to design the small-molecule pure antagonists TDI-4161 and TDI-3761. Both compounds inhibit αVβ3-mediated cell adhesion to αVβ3 ligands, but do not induce the conformational change as judged by antibody binding, electron microscopy, X-ray crystallography, and receptor priming studies. Both compounds demonstrated the favorable property of inhibiting bone resorptionin vitro, supporting potential value in treating osteoporosis. Neither, however, had the unfavorable property of the αVβ3 antagonist cilengitide of paradoxically enhancing aortic sprout angiogenesis at concentrations below its IC50, which correlates with cilengitide’s enhancement of tumor growthin vivo.Significance StatementαVβ3 is a potential therapeutic target for several important human diseases, but there are currently no αVβ3 antagonists approved for human therapy. Current candidates are primarily based on the Arg-Gly-Asp (RGD) motif and act as partial agonists in that they induce αVβ3 to undergo a conformational change that converts it into a high-affinity ligand-binding state. We have used structure-guided design to produce pure small-molecule αVβ3 antagonists that do not induce the conformational change as judged by protein crystallography, electron microscopy, and receptor priming. These compounds inhibit αVβ3-mediated bone resorptionin vitro, but unlike the partial agonist cilengitide, do not enhance angiogenesis at low doses, a property that correlates with low-dose cilengitide’s enhancement of tumor growthin vivo. These pure αVβ3 antagonists can help define αVβ3’s role in animal models. If they demonstrate benefits over partial agonists in these model systems, they may be appropriate to consider for human therapy.

scholarly journals A novel radioiodinated high affinity ligand for the D2 -dopamine receptor

FEBS Letters ◽  
1984 ◽  
Vol 176 (2) ◽  
pp. 436-440 ◽  
Author(s):  
Nourdine Amlaiky ◽  
Brian F. Kilpatrick ◽  
Marc G. Caron
Keyword(s):  
Dopamine Receptor ◽  
D2 Dopamine Receptor ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals High-Affinity Ligand Probes of CD22 Overcome the Threshold Set bycisLigands to Allow for Binding, Endocytosis, and Killing of B Cells

2006 ◽  
Vol 177 (5) ◽  
pp. 2994-3003 ◽  
Author(s):  
Brian E. Collins ◽  
Ola Blixt ◽  
Shoufa Han ◽  
Bao Duong ◽  
Hongyi Li ◽  
...  
Keyword(s):  
B Cells ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals RS-45041-190: a selective, high-affinity ligand for I2 imidazoline receptors

1995 ◽  
Vol 116 (2) ◽  
pp. 1737-1744 ◽  
Author(s):  
C.M. Brown ◽  
A.C. MacKinnon ◽  
W.S. Redfern ◽  
A. Williams ◽  
C. Linton ◽  
...  
Keyword(s):  
Imidazoline Receptors ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

Cortistatin A is a High-Affinity Ligand of Protein Kinases ROCK, CDK8, and CDK11

2009 ◽  
Vol 48 (47) ◽  
pp. 8952-8957 ◽  
Author(s):  
Victor J. Cee ◽  
David Y.-K. Chen ◽  
Matthew R. Lee ◽  
K. C. Nicolaou
Keyword(s):  
Protein Kinases ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ)

1995 ◽  
Vol 270 (22) ◽  
pp. 12953-12956 ◽  
Author(s):  
Jürgen M. Lehmann ◽  
Linda B. Moore ◽  
Tracey A. Smith-Oliver ◽  
William O. Wilkison ◽  
Timothy M. Willson ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand
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