IgNAR antibody: Structural features, diversity and applications

Khalid, Zunera; Chen, Yulei; Yu, Du; Abbas, Misbah; Ma, Huan; Naz, Zara; Mengist, Hylemariam Mihiretie; Cao, Min‐Jie; Jin, Tengchuan

doi:10.1016/j.fsi.2022.01.027

Cited by 14 publications

(24 citation statements)

References 88 publications

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“…The amino acid sequences of the seven clones were regionally delineated as shown in Figure 4. The conserved cysteine residues in FR1, FR3b, and the conserved tryptophan residues in FR2 play an essential role in the folded structure of IgNAR, unchanged for hundreds of millions of years, 46 and the homology of the obtained clones with new antigen receptors from Ginglymostoma cirratum was further verified. The CDR3 is the most critical source of VNARs diversity and determinant of antigen‐binding specificity, so the variability of the sequences we obtained was mainly concentrated in the CDR3 47 .…”

Section: Resultsmentioning

confidence: 87%

The specific biopanning of single‐domain antibody against haptens based on a functionalized cryogel

Zhang

Liu

Han

et al. 2022

J of Molecular Recognition

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Phage display technology is commonly applied for high-throughput screening of single-domain antibodies (sdAbs), and the problem of non-specific adsorption caused by carrier proteins seriously affects the biopanning of single-domain antibodies specific to haptens. In this paper, enrofloxacin (ENR)-functionalized cryogels were prepared by the ethylenediamine (EDA) and carbodiimide methods for application in the biopanning of ENR-specific phages. To improve the efficiency of biopanning, double blocking, a wash solution flow rate of 1 mL/min, and phage pre-incubation were applied to the biopanning process through single-factor experiments. Results of flat colony counting showed that the phage output of AG-ENR cryogels was 15 times higher than that of AG cryogels for the same input amount. And seven complete sequences of ENR-specific shark sdAbs were obtained by monoclonal phage ELISA and sequence alignment. All these results indicate that functionalized cryogels could be used as a novel and efficient method for phage biopanning for single-domain antibodies to haptens.

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Section: Resultsmentioning

confidence: 87%

The specific biopanning of single‐domain antibody against haptens based on a functionalized cryogel

Zhang

Liu

Han

et al. 2022

J of Molecular Recognition

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“…V H Hs are found on the heavy-chain antibodies (HCAbs, naturally devoid of light chains) produced by camelids. − Since the V H H domain is not complexed with other antibody domains, its surface tends to be much more hydrophilic than those of V H and V L . Besides camelids, cartilaginous fishes such as sharks also produce a distinct type of heavy-chain antibodies containing a single variable region, V NAR , which could also serve as therapeutic sdAbs. , These smaller frameworks of individual antibody domains have been widely used in antitumor immunotherapy, mainly through immune checkpoint antigen blockade and chimeric antigen receptor (CAR)-T cell engineering. , Very recently, Harmon et al constructed a high-diversity nanobody bacteriophage library and identified nanobodies with high affinity to SARS-CoV-2 S protein and receptor-binding domain (RBD). These nanobodies were subsequently used to prevent the SARS-CoV-2 spike protein from binding to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2) expressed on host cells, leading to the neutralization of viral infection.…”

Section: Is There a Place For Antibody-based Therapeutics?mentioning

confidence: 99%

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

et al. 2023

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The high selectivity and affinity of antibodies toward their antigens have made them a highly valuable tool in disease therapy, diagnosis, and basic research. A plethora of chemical and genetic approaches have been devised to make antibodies accessible to more “undruggable” targets and equipped with new functions of illustrating or regulating biological processes more precisely. In this Review, in addition to introducing how naked antibodies and various antibody conjugates (such as antibody-drug conjugates, antibody-oligonucleotide conjugates, antibody-enzyme conjugates, etc.) work in therapeutic applications, special attention has been paid to how chemistry tools have helped to optimize the therapeutic outcome (i.e., with enhanced efficacy and reduced side effects) or facilitate the multifunctionalization of antibodies, with a focus on emerging fields such as targeted protein degradation, real-time live-cell imaging, catalytic labeling or decaging with spatiotemporal control as well as the engagement of antibodies inside cells. With advances in modern chemistry and biotechnology, well-designed antibodies and their derivatives via size miniaturization or multifunctionalization together with efficient delivery systems have emerged, which have gradually improved our understanding of important biological processes and paved the way to pursue novel targets for potential treatments of various diseases.

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“…The most distinctive feature of the VNAR domain is the deletion of C’ and C’’ strands that typically comprise the CDR2 region as the somatic mutations result ( 15 ), making it only consisted of 8 β-strands, becoming the most minor antigen binding domain naturally ( 33 , 34 ) ( Figure 1C ). A conserved disulfide bond connects two β-strands between FR1 (22Cys) and FR3 (83Cys) ( 35 ) [in some studies numbered as 21Cys & 82Cys ( 20 )]. The absence of the CDR2 region is compensated by two loops, known as hypervariable region 2 region (HV2) and hypervariable region 4 region (HV4), with a high diversity of amino acids.…”

Section: Structural Features Of Sdabsmentioning

confidence: 99%

“…( 19 ) and Khalid et al. ( 20 ) looked forward to the potential of sdAbs in the field of disease treatment, clinical diagnosis and immune detection, respectively. Meanwhile, Leow et al.…”

Section: Introductionmentioning

confidence: 99%

Research progress on unique paratope structure, antigen binding modes, and systematic mutagenesis strategies of single-domain antibodies

et al. 2022

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Single-domain antibodies (sdAbs) showed the incredible advantages of small molecular weight, excellent affinity, specificity, and stability compared with traditional IgG antibodies, so their potential in binding hidden antigen epitopes and hazard detection in food, agricultural and veterinary fields were gradually explored. Moreover, its low immunogenicity, easy-to-carry target drugs, and penetration of the blood-brain barrier have made sdAbs remarkable achievements in medical treatment, toxin neutralization, and medical imaging. With the continuous development and maturity of modern molecular biology, protein analysis software and database with different algorithms, and next-generation sequencing technology, the unique paratope structure and different antigen binding modes of sdAbs compared with traditional IgG antibodies have aroused the broad interests of researchers with the increased related studies. However, the corresponding related summaries are lacking and needed. Different antigens, especially hapten antigens, show distinct binding modes with sdAbs. So, in this paper, the unique paratope structure of sdAbs, different antigen binding cases, and the current maturation strategy of sdAbs were classified and summarized. We hope this review lays a theoretical foundation to elucidate the antigen-binding mechanism of sdAbs and broaden the further application of sdAbs.

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IgNAR antibody: Structural features, diversity and applications

Cited by 14 publications

References 88 publications

The specific biopanning of single‐domain antibody against haptens based on a functionalized cryogel

The specific biopanning of single‐domain antibody against haptens based on a functionalized cryogel

The Dawn of a New Era: Targeting the “Undruggables” with Antibody-Based Therapeutics

Research progress on unique paratope structure, antigen binding modes, and systematic mutagenesis strategies of single-domain antibodies

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