Indolizine-Based Scaffolds as Efficient and Versatile Tools: Application to the Synthesis of Biotin-Tagged Antiangiogenic Drugs

ACS Omega
Marie Arvin-BerodMartine Demeunynck

Abstract

We describe the design and optimization of polyfunctional scaffolds based on a fluorescent indolizine core derivatized with various orthogonal groups (amines, esters, oximes, alkynes, etc.). To show one application as tools in biology, the scaffold was used to prepare drug-biotin conjugates that were then immobilized onto avidin-agarose for affinity chromatography. More specifically, the antiangiogenic drug COB223, whose mechanism of action remained unclear, was chosen as a proof-of-concept drug. The drug-selective discrimination of proteins observed after elution of the cell lysates through the affinity columns, functionalized either with the biologically active COB223 or a structurally related inactive analogue (COB236), is a clear indication that the presence of the indolizine core does not limit drug-protein interaction and confirms the usefulness of the indolizine scaffold. Furthermore, the separation of COB223-interacting proteins from human placental extracts unveiled unanticipated protein targets belonging to the family of regulatory RNA-binding proteins, which opens the way to new hypotheses on the mode of action of this antiangiogenic drug.

References

Sep 22, 2005·Bioconjugate Chemistry·Rajarathnam E ReddyJohn K Thottathil
May 14, 2008·Nature Reviews. Genetics·Seung Yon RheeSorin Draghici
Oct 15, 2008·Molecular Cancer Therapeutics·Yuexing ZhangAnne W Hamburger
Jan 2, 2009·Langmuir : the ACS Journal of Surfaces and Colloids·Hideo TokuhisaLane A Baker
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Sep 23, 2011·European Journal of Medicinal Chemistry·Girija S Singh, Edward E Mmatli
Nov 22, 2011·Organic & Biomolecular Chemistry·David M BealLyn H Jones
Mar 12, 2013·Organic & Biomolecular Chemistry·Guillaume ViaultAnthony Romieu
Apr 30, 2013·Macromolecular Rapid Communications·Anja S GoldmannChristopher Barner-Kowollik
Jun 8, 2013·Proteomics·Maria G CasabonaYohann Couté
Aug 26, 2014·Biotechnology and Applied Biochemistry·Mireille EngelenFlavia Nastri
Sep 23, 2014·Chemistry & Biology·Craig S McKay, M G Finn
Mar 16, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Simon BonteMartine Demeunynck
Apr 22, 2016·Natural Product Reports·M H Wright, S A Sieber
Jul 28, 2016·Nature Reviews. Molecular Cell Biology·Michael SimonsLena Claesson-Welsh

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Methods Mentioned

BETA
electrophoresis
affinity purification

Software Mentioned

DAVID
DAVID Bioinformatics Resource
Proline
Mascot

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Pediatric Clinics of North America
J Krasner
Cold Spring Harbor Symposia on Quantitative Biology
L M ParkerM B Mathews
Methods in Molecular Biology
Birgit Ritter, Marc R Reboll
© 2022 Meta ULC. All rights reserved