Chemical Tools to Monitor and Manipulate the Adaptive Immune System

Kodadek, Thomas

doi:10.1016/j.chembiol.2014.07.009

Cited by 14 publications

(24 citation statements)

References 47 publications

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“…The significance of identifying antigens, antigen surrogates (i.e. antigen-mimics that can be chemically distinct from the antigens that elicited an antibody response) and immunosignatures [29] for disease diagnosis is being increasingly recognized. Additionally, mapping the serum antigen reactivity profile in a comprehensive manner is key to understanding which environmental exposures play a more dominant role in shaping humoral immunity.…”

Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

“…Earlier methods for antigen discovery include the use of peptide libraries either immobilized in array format or displayed on M13 phage and serological analysis of recombinant cDNA expression libraries (SEREX), which employs cDNA libraries from tumor tissues for cancer antigen discovery and finally, antigen arrays [29,30•,31,32]. More recently advances in library screening methodologies and separately, in high throughput gene and peptide synthesis technologies have led to an explosion of high-resolution methods for the discovery of autoantigens and antigen surrogates.…”

Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

“…In an alternative approach very high density printed arrays of synthetic random peptide arrays were used for immunosignature discovery and were reported to exhibit higher accuracy than tiled peptide epitope arrays [37,38]. Since peptides may not be able to capture antibodies that bind to post-translational modifications and conformational epitopes Kodadek and coworkers pioneered the use of libraries of unnatural molecules and specifically peptoids (N-substituted oligoglycine polymers) for the discovery of surrogate antigen biomarkers from patient sera [29,39]. Other powerful methods that are currently used for antigen discovery include antigen microarrays [40,41], nucleic acid programmable protein arrays (NAPPAs) produced using in-vitro transcription/translation[42], peptide arrays [43] or finally arrays based on a different targets such as DNA, peptides and recombinant/native proteins [44].…”

Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

See 2 more Smart Citations

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

Wine

Horton

Ippolito

et al. 2015

Current Opinion in Immunology

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The ensemble of antibodies found in serum and secretions represents the key adaptive component of B-cell mediated humoral immunity. The antibody repertoire is shaped by the historical record of exposure to exogenous factors such as pathogens and vaccines, as well as by endogenous host-intrinsic factors such as genetics, self-antigens, and age. Thanks to very recent technology advancements it is now becoming possible to identify and quantify the individual antibodies comprising the serological repertoire. In parallel, the advent of high throughput methods for antigen and immunosignature discovery opens up unprecedented opportunities to transform our understanding of numerous key questions in adaptive humoral immunity, including the nature and dynamics of serological memory, the role of polyspecific antibodies in health and disease and how protective responses to infections or vaccine challenge arise. Additionally, these technologies also hold great promise for therapeutic antibody and biomarker discovery in a variety of settings

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Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

Section: Antibody Serology: Future Directionsmentioning

confidence: 99%

See 1 more Smart Citation

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

Wine

Horton

Ippolito

et al. 2015

Current Opinion in Immunology

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“…We have termed synthetic ligands for the antigen-binding sites of immune receptors “epitope surrogates” 27 . We prefer this term to “epitope mimics” because the latter suggests that the synthetic ligand will bind the immune receptor in the same way as the native epitope.…”

Section: Introductionmentioning

confidence: 99%

Chemical Tools To Monitor and Manipulate Adaptive Immune Responses

2016

Self Cite

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Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of “reawakening” the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between “good” and “bad” immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensivel y monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field.

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“…Peptoids have been proposed as an avenue for manipulation of antigen-specific immune responses by functioning as "antigen surrogates" to amplify a weak immune response or weaken a deleterious immune response through competition. Peptoids that incorporate backbone chirality to restrict conformation have been selected for high binding affinity and selectivity to the antigen-binding site of therapeutically relevant antibodies, demonstrating the feasibility of this approach 48 . In a different approach, peptoid mimics of catalase and superoxide dismutase have been designed to mitigate the impact of oxidative stress, an integral component of inflammation.…”

Section: Peptoids For Attenuation Of Neuroinflammationmentioning

confidence: 99%

Peptoids: Emerging Therapeutics for Neurodegeneration

Moss¹

2017

J Neurol Neuromedicine

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In recent decades, the increasing prevalence of age-associated neurodegenerative diseases has underscored the need for targeted therapeutic strategies and novel diagnostics. Peptide-based neurotherapeutics offer high specificity and tolerability but are limited by proteolytic degradation in vivo. Peptoids, or N-substituted glycines, are versatile peptidomimetics that evade proteolytic degradation yet maintain many qualities that render peptides attractive neurotherapeutic candidates. These molecules may be engineered to their application through modifications that enhance structural stability and reactivity and can withstand various physiological stressors to retain their intended function within anomalous microenvironments.Peptoids generally demonstrate greater cellular permeability than their corresponding peptides, are less immunogenic, and can be administered intranasally, all properties that enhance their potential as neurotherapeutics. Peptoids have primarily been explored as aggregation inhibitors to prevent the deleterious protein plaque deposition associated with several neurodegenerative disorders. However, novel research has uncovered the potential of peptoids toward additional neurotherapeutic applications. Peptoids can modulate cell signaling pathways involved in axonal function and current modulation and can block cell signaling events associated with apoptosis. In addition, these peptidomimetics are able to function as anti-inflammatory agents via multiple mechanisms. Moreover, the versatility and low cost of peptoids render them ideal instruments in biomarker detection, discovery, and imaging. This mini-review explores these diverse applications of peptoids within the context of neurodegenerative disease.

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Chemical Tools to Monitor and Manipulate the Adaptive Immune System

Cited by 14 publications

References 47 publications

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

Serology in the 21st century: the molecular-level analysis of the serum antibody repertoire

Chemical Tools To Monitor and Manipulate Adaptive Immune Responses

Peptoids: Emerging Therapeutics for Neurodegeneration

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