Discovery of Diphenylmethanepropionic and Dihydrostilbeneacetic Acids as Antagonists of the Integrin αvβ3

Nagarajan, Srinivasan; Meyer, Jane M.; Miyashiro, Julie M.; Engleman, V. Wayne; Freeman, Sandra K.; Griggs, David W.; Klover, Jon A.; Nickols, G. Allen

doi:10.1111/j.1747-0285.2006.00344.x

Cited by 6 publications

(3 citation statements)

References 23 publications

(26 reference statements)

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“…In summary, we have developed a palladium-catalyzed arylation reaction producing five- to seven-membered benzolactones via a sequential carbon−carbon bond cleavage/formation process. This reaction provides an access to 2,4-, 3,4-, and 4,4-diarylbutyric acid derivatives, which are intermediates in the synthesis of natural products and pharmaceuticals …”

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confidence: 99%

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

2008

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3-(2-Hydroxyphenyl)cyclobutanones react with aryl bromides in the presence of palladium catalysts to afford 4-arylmethyl-3,4-dihydrocoumarins in high yields through a sequence involving carbon-carbon bond cleavage and formation. In the case of the reaction with 2-(2-hydroxyphenyl)cyclobutanones, five- or seven-membered lactones were produced depending on the presence of an additional substituent at the 2-position.

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confidence: 99%

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

2008

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“…This difference may be explained by the conformational rigidity of the biphenyl group between the RGD peptide and NOTA chelate. The biphenyl group provides structural rigidity to the molecule . Incorporating flexible molecules, such as polyethylene glycol, do not increase hydrophilicity but do decrease binding affinity …”

Section: Resultsmentioning

confidence: 99%

Synthesis and Preliminary Evaluation of ⁶⁸Ga‐NOTA‐Biphenyl‐c(RGDyK) for the Quantification of Integrin α_vβ₃

Shin

Jung

Park

et al. 2017

Bulletin Korean Chem Soc

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Arginine‐glycine‐aspartate (RGD) peptide binds to the integrin αvβ3, which plays a crucial role in tumor angiogenesis and metastasis. Previously developed 68Ga‐labeled cyclic RGD peptides are rapidly excreted from the circulatory system. In the present study, we developed a 68Ga‐labeled cyclic RGD peptide with a biphenyl group between the chelator and RGD peptide, i.e., 68Ga‐NOTA‐biphenyl‐c(RGDyK). Then, we performed the comparison with the reference compound, i.e., 68Ga‐NOTA‐c(RGDyK). 68Ga‐NOTA‐biphenyl‐c(RGDyK) was 37% less hydrophilic than 68Ga‐NOTA‐c(RGDyK). For positron emission tomography imaging, 68Ga‐NOTA‐biphenyl‐c(RGDyK) had a longer retention time and showed a higher signal‐to‐noise ratio in tumors than 68Ga‐NOTA‐c(RGDyK). However, the biphenyl‐radiopeptide displayed the relatively high non‐specific binding. From these perspectives, incorporation of the biphenyl group to the RGD generates pros and cons.

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“…Integrin’s antagonists are mostly oligopeptides or larger peptides [ 20 , 21 ], which are often promising for therapeutic purposes [ 22 ]. Occasionally, small ligands can also behave as allosteric integrin inhibitors [ 23 , 24 , 25 , 26 , 27 ] and are also frequently used as pharmaceuticals. A recent example of a small, non-peptide xenobiotic found to exert a unique and specific integrin-targeting activity is a phosphonomethylamino acid derivative, glyphosate [ N -(phosphonomethyl)glycine] [ 28 ].…”

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confidence: 99%

Comparative Assessment of the Inhibitory Potential of the Herbicide Glyphosate and Its Structural Analogs on RGD-Specific Integrins Using Enzyme-Linked Immunosorbent Assays

Gémes

Takács

Székács

et al. 2022

IJMS

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Transmembrane glycoprotein integrins play crucial roles in biochemical processes, and by their inhibition or activation, different signal pathways can be disrupted, leading to abnormal physiological functions. We have previously demonstrated the inhibitory effect of glyphosate herbicide’s active ingredient on cell adhesion and its αvβ3 integrin antagonist effect. Therefore, it appeared particularly exciting to investigate inhibition of glyphosate and its metabolites on a wider range of Arg-Gly-Asp (RGD) binding integrins, namely αvβ3, α5β1 and αllbβ3. Thus, the purpose of this study was to assess how extended the inhibitory effect observed for glyphosate on the integrin αvβ3 is in terms of other RGD integrins and other structurally or metabolically related derivatives of glyphosate. Five different experimental setups using enzyme-linked immunosorbent assays were applied: (i) αvβ3 binding to a synthetic polymer containing RGD; (ii) αvβ3 binding to its extracellular matrix (ECM) protein, vitronectin; (iii) α5β1 binding to the above polymer containing RGD; (iv) αllbβ3 binding to its ECM protein, fibrinogen and (v) αvβ3 binding to the SARS-CoV-2 spike protein receptor binding domain. Total inhibition of αvβ3 binding to RGD was detected for glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), as well as for acetylglycine on α5β1 binding to RGD.

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Discovery of Diphenylmethanepropionic and Dihydrostilbeneacetic Acids as Antagonists of the Integrin α_vβ₃

Cited by 6 publications

References 23 publications

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

Synthesis and Preliminary Evaluation of ⁶⁸Ga‐NOTA‐Biphenyl‐c(RGDyK) for the Quantification of Integrin α_vβ₃

Comparative Assessment of the Inhibitory Potential of the Herbicide Glyphosate and Its Structural Analogs on RGD-Specific Integrins Using Enzyme-Linked Immunosorbent Assays

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Discovery of Diphenylmethanepropionic and Dihydrostilbeneacetic Acids as Antagonists of the Integrin αvβ3

Cited by 6 publications

References 23 publications

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

Palladium-Catalyzed Sequential Carbon−Carbon Bond Cleavage/Formation Producing Arylated Benzolactones

Synthesis and Preliminary Evaluation of 68Ga‐NOTA‐Biphenyl‐c(RGDyK) for the Quantification of Integrin αvβ3

Comparative Assessment of the Inhibitory Potential of the Herbicide Glyphosate and Its Structural Analogs on RGD-Specific Integrins Using Enzyme-Linked Immunosorbent Assays

Contact Info

Product

Resources

About

Discovery of Diphenylmethanepropionic and Dihydrostilbeneacetic Acids as Antagonists of the Integrin α_vβ₃

Synthesis and Preliminary Evaluation of ⁶⁸Ga‐NOTA‐Biphenyl‐c(RGDyK) for the Quantification of Integrin α_vβ₃