Synthetic Peptide Antibodies as TNF‐α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF‐α in THP‐1 Derived Macrophages

León, Cecilia; Kalacas, Noel Angelo; Mier, Alejandra; Sakhaii, Peyman; Merlier, Franck; Prost, Élise; Maffucci, Irene; Montagna, Valentina; Mora-Radó, Helena; Dhal, Pradeep K.; Bui, Bernadette Tse Sum; Haupt, Karsten

doi:10.1002/ange.202306274

Cited by 3 publications

(1 citation statement)

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“…The imprint or epitope is then removed from the resulting polymer to reveal a binding site for the target. Several recent notable examples of this approach are given. , …”

Section: Introductionmentioning

confidence: 99%

Design of an Anti-HMGB1 Synthetic Antibody for In Vivo Ischemic/Reperfusion Injury Therapy

Koide,

Kiyokawa,

Okishima

et al. 2023

J. Am. Chem. Soc.

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High-mobility group box 1 (HMGB1) is a multifunctional protein. Upon injury or infection, HMGB1 is passively released from necrotic and activated dendritic cells and macrophages, where it functions as a cytokine, acting as a ligand for RAGE, a major receptor of innate immunity stimulating inflammation responses including the pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Blocking the HMGB1/RAGE axis offers a therapeutic approach to treating these inflammatory conditions. Here, we describe a synthetic antibody (SA), a copolymer nanoparticle (NP) that binds HMGB1. A lightly cross-linked N-isopropylacrylamide (NIPAm) hydrogel copolymer with nanomolar affinity for HMGB1 was selected from a small library containing trisulfated 3,4,6S-GlcNAc and hydrophobic N-tert-butylacrylamide (TBAm) monomers. Competition binding experiments with heparin established that the dominant interaction between SA and HMGB1 occurs at the heparin-binding domain. In vitro studies established that anti-HMGB1-SA inhibits HMGB1-dependent ICAM-1 expression and ERK phosphorylation of HUVECs, confirming that SA binding to HMGB1 inhibits the proteins’ interaction with the RAGE receptor. Using temporary middle cerebral artery occlusion (t-MCAO) model rats, anti-HMGB1-SA was found to accumulate in the ischemic brain by crossing the blood–brain barrier. Significantly, administration of anti-HMGB1-SA to t-MCAO rats dramatically reduced brain damage caused by cerebral ischemia/reperfusion. These results establish that a statistical copolymer, selected from a small library of candidates synthesized using an “informed” selection of functional monomers, can yield a functional synthetic antibody. The knowledge gained from these experiments can facilitate the discovery, design, and development of a new category of drug.

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“…The imprint or epitope is then removed from the resulting polymer to reveal a binding site for the target. Several recent notable examples of this approach are given. , …”

Section: Introductionmentioning

confidence: 99%

Design of an Anti-HMGB1 Synthetic Antibody for In Vivo Ischemic/Reperfusion Injury Therapy

Koide,

Kiyokawa,

Okishima

et al. 2023

J. Am. Chem. Soc.

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Molecularly imprinted polymers (MIPs) for SARS-CoV-2 omicron variant inhibition: An alternative approach to address the challenge of emerging zoonoses

Dattilo,

Patitucci,

Motta

et al. 2025

Colloids and Surfaces B: Biointerfaces

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Boosting Electrochemical Sensing Performances Using Molecularly Imprinted Nanoparticles

Gagliani,

Di Giulio,

Asif

et al. 2024

Biosensors

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Nanoparticles of molecularly imprinted polymers (nanoMIPs) combine the excellent recognition ability of imprinted polymers with specific properties related to the nanosize, such as a high surface-to-volume ratio, resulting in highly performing recognition elements with surface-exposed binding sites that promote the interaction with the target and, in turn, binding kinetics. Different synthetic strategies are currently available to produce nanoMIPs, with the possibility to select specific conditions in relation to the nature of monomers/templates and, importantly, to tune the nanoparticle size. The excellent sensing properties, combined with the size, tunability, and flexibility of synthetic protocols applicable to different targets, have enabled the widespread use of nanoMIPs in several applications, including sensors, imaging, and drug delivery. The present review summarizes nanoMIPs applications in sensors, specifically focusing on electrochemical detection, for which nanoMIPs have been mostly applied. After a general survey of the most widely adopted nanoMIP synthetic approaches, the integration of imprinted nanoparticles with electrochemical transducers will be discussed, representing a key step for enabling a reliable and stable sensor response. The mechanisms for electrochemical signal generation will also be compared, followed by an illustration of nanoMIP-based electrochemical sensor employment in several application fields. The high potentialities of nanoMIP-based electrochemical sensors are presented, and possible reasons that still limit their commercialization and issues to be resolved for coupling electrochemical sensing and nanoMIPs in an increasingly widespread daily-use technology are discussed.

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Synthetic Peptide Antibodies as TNF‐α Inhibitors: Molecularly Imprinted Polymer Nanogels Neutralize the Inflammatory Activity of TNF‐α in THP‐1 Derived Macrophages

Cited by 3 publications

References 47 publications

Design of an Anti-HMGB1 Synthetic Antibody for In Vivo Ischemic/Reperfusion Injury Therapy

Design of an Anti-HMGB1 Synthetic Antibody for In Vivo Ischemic/Reperfusion Injury Therapy

Molecularly imprinted polymers (MIPs) for SARS-CoV-2 omicron variant inhibition: An alternative approach to address the challenge of emerging zoonoses

Boosting Electrochemical Sensing Performances Using Molecularly Imprinted Nanoparticles

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