Effects of serum matrix on molecular interactions between drugs and target proteins revealed by giant magneto-resistive bio-sensing techniques

Saito, Toshiro; Momiyama, Masayoshi; Manri, Chihiro; Heng, Yu; Choudhury, Kalidip; Osterfeld, Sebastian J.; Nakasawa, Takashi

doi:10.1016/j.jpba.2021.114015

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…The SPR and BLI platforms have severe limitations due to the serum matrix, likely an interference with the optical signals and cannot distinguish between specific binding and non-specific binding of serum proteins. 10,20,21 As a result, negative signals are sometimes observed after reference subtraction, or the derived kinetics parameters are not reliable, even if the binding traces can be fit. The SPR platform is not able to generate suitable curves in as little as 10% serum.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, our colleagues used the GMR platform to demonstrate that even small amounts of a serum-based product had a profound effect on the binding of protein kinase A with its small molecule target quercetin. 10 In those experiments, the serum-based product 27 , had little effect on two antibody drug-target pairs, infliximab/TNFα and bevacizumab/VEGF. Thus, the processed serum-based product may not be an accurate substitute for subject serum.…”

Section: Discussionmentioning

confidence: 97%

“…We and our colleagues have previously shown that the GMR platform can be used to evaluate the serum matrix effects on the interactions between targets and drug molecules. 10 Some pairs, like protein kinase A and its small molecule target quercetin, were greatly affected by the presence of a commercial serum-based product. In contrast, the commercial serum-based product had little effect on two antibody drug-target pairs: infliximab-TNFa and bevacizumab-VEGF.…”

Section: Introductionmentioning

confidence: 99%

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Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum

Yao

Heng

Kantor

et al. 2021

Preprint

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The ability to characterize the binding kinetics of drug-target interactions in a biologically relevant matrix, such as serum or plasma, remains a fundamental challenge in drug discovery. We apply a novel label-based giant magnetoresistance (GMR) biosensor platform to measure protein binding kinetics and affinities of drug-target pairs in buffer and different levels of serum. Specifically, we evaluate three well-established immune checkpoint inhibitors, pembrolizumab, nivolumab and atezolizumab and compare the results with label-free kinetic platforms: surface plasmon resonance (SPR) and bio-layer interferometry (BLI). Labeling of analytes does not affect their association and dissociation rates (on and off rates) from GMR biosensors which enables kinetic measurements in biologically relevant matrices. Only the GMR biossensors is consistently suitable for measuring binding kinetics in up to 80% serum. The faster and different off-rates of the three immune checkpoint inhibitors in the presence of serum should be considered when modeling their pharmacological performance.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum

Yao

Heng

Kantor

et al. 2021

Preprint

Self Cite

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Nano‐Photonic Crystal D‐Shaped Fiber Devices for Label‐Free Biosensing at the Attomolar Limit of Detection

Del Villar,

Gonzalez‐Valencia,

Kwietniewski

et al. 2024

Advanced Science

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Maintaining both high sensitivity and large figure of merit (FoM) is crucial in regard to the performance of optical devices, particularly when they are intended for use as biosensors with extremely low limit of detection (LoD). Here, a stack of nano‐assembled layers in the form of 1D photonic crystal, deposited on D‐shaped single‐mode fibers, is created to meet these criteria, resulting in the generation of Bloch surface wave resonances. The increase in the contrast between high and low refractive index (RI) nano‐layers, along with the reduction of losses, enables not only to achieve high sensitivity, but also a narrowed resonance bandwidth, leading to a significant enhancement in the FoM. Preliminary testing for bulk RI sensitivity is carried out, and the effect of an additional nano‐layer that mimics a biological layer where binding interactions occur is also considered. Finally, the biosensing capability is assessed by detecting immunoglobulin G in serum at very low concentrations, and a record LoD of 70 aM is achieved. An optical fiber biosensor that is capable of attaining extraordinarily low LoD in the attomolar range is not only a remarkable technical outcome, but can also be envisaged as a powerful tool for early diagnosis of diseases.

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Emerging affinity methods for protein-drug interaction analysis

Zheng,

Zhu,

Zhao

et al. 2024

Journal of Pharmaceutical and Biomedical Analysis

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Effects of serum matrix on molecular interactions between drugs and target proteins revealed by giant magneto-resistive bio-sensing techniques

Cited by 5 publications

References 12 publications

Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum

Differential Binding Kinetics for Evaluating Immune Checkpoint Inhibitors in Serum

Nano‐Photonic Crystal D‐Shaped Fiber Devices for Label‐Free Biosensing at the Attomolar Limit of Detection

Emerging affinity methods for protein-drug interaction analysis

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