Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG

Gavrilyuk, Julia; Ban, Hyun Seung; Uehara, Hisatoshi; Sirk, Shannon J.; Saye-Francisco, Karen L.; Cuevas, Angélica; Zablowsky, Elise; Oza, Avinash; Seaman, Michael S.; Burton, Dennis R.; Barbas, Carlos F.

doi:10.1128/jvi.03146-12

Cited by 20 publications

(19 citation statements)

References 44 publications

(47 reference statements)

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“…Variations on this reaction have also been used to label tyrosine aromatic rings with moderate rate and high selectivity (Table 3, entries 5–6) (Bruckman et al, 2008; Hooker et al, 2004; Jones et al, 2012; Schlick et al, 2005). The resulting azo intermediate can be processed in a number of ways, such as by oxidation to o -iminoquinone for hetero-Diels-Alder reaction (Hooker et al, 2004), or simply kept as a connector to another functional group that can be addressed by a second bioorthogonal reaction (such as oxime formation) (Gavrilyuk et al, 2013; Schlick et al, 2005). Similarly, a three component Mannich reaction between tyrosine and imines formed from aldehydes and electron rich anilines has also been described (entry 7) (Joshi et al, 2004), although it is relatively slow and requires a large excess of regents (McFarland et al, 2008; Romanini and Francis, 2007).…”

Section: B Bioorthogonal Conjugation Strategies and Applicationsmentioning

confidence: 99%

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

McKay

Finn

2014

Chemistry & Biology

643

555

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The selective chemical modification of biological molecules drives a good portion of modern drug development and fundamental biological research. While a few early examples of reactions that engage amine and thiol groups on proteins helped establish the value of such processes, the development of reactions that avoid most biological molecules so as to achieve selectivity in desired bond-forming events has revolutionized the field. We provide an update on recent developments in bioorthogonal chemistry that highlights key advances in reaction rates, biocompatibility, and applications. While not exhaustive, we hope this summary allows the reader to appreciate the rich continuing development of good chemistry that operates in the biological setting.

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Section: B Bioorthogonal Conjugation Strategies and Applicationsmentioning

confidence: 99%

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

McKay

Finn

2014

Chemistry & Biology

643

555

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“…However, experiments with N-acyl methylamides of histidine, serine, cysteine, tryptophan and lysine revealed reactivity the latter two towards cyclic diazodicarboxamid. In addition histidine, tryptophan and unoxidized cysteine exhibited reactivity towards a diazonium hexafluorophosphate derivative [69,70]. Even if both reagents exhibit a high chemoselectivity for tyrosine, side reactions with other amino acids are inevitable.…”

Section: Conjugation Via Tyrosinementioning

confidence: 99%

Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

2015

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Monoclonal antibodies (mAbs) and their derivatives are currently the fastest growing class of therapeutics. Even if naked antibodies have proven their value as successful biopharmaceuticals, they suffer from some limitations. To overcome suboptimal therapeutic efficacy, immunoglobulins are conjugated with toxic payloads to form antibody drug conjugates (ADCs) and with chelating systems bearing therapeutic radioisotopes to form radioimmunoconjugates (RICs). Besides their therapeutic applications, antibody conjugates are also extensively used for many in vitro assays. A broad variety of methods to functionalize antibodies with various payloads are currently available. The decision as to which conjugation method to use strongly depends on the final purpose of the antibody conjugate. Classical conjugation via amino acid residues is still the most common method to produce antibody conjugates and is suitable for most in vitro applications. In recent years, however, it has become evident that antibody conjugates, which are generated via site-specific conjugation techniques, possess distinct advantages with regard to in vivo properties. Here, we give a comprehensive overview on existing and emerging strategies for the production of covalent and non-covalent antibody conjugates.

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“…Many such strategies exist and include conjugation of antiviral mAbs or mAb-based molecules to: 1) cholesterol to enhance potency through cholesterol-mediated interactions with the viral membrane [264], 2) small molecule inhibitors of viral entry to enhance neutralization potency [265], 3) CD4 domains to expose CD4-inducible epitopes on viral Env [266–268], and 4) recombinant immunotoxins to enhance cytotoxicity [269–271]. In this review, we focus on the recent development of various bispecific formats (Figure 3) to combat viral resistance and T-cell engaging molecules/cells to eradicate latent HIV reservoirs (summarized in Table 3).…”

Section: Adding Non-native Functions To Bnabsmentioning

confidence: 99%

Engineering broadly neutralizing antibodies for HIV prevention and therapy

Hua

Ackerman

2016

Advanced Drug Delivery Reviews

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A combination of advances spanning from isolation to delivery of potent HIV-specific antibodies have begun to revolutionize understandings of antibody-mediated antiviral activity. As a result, the set of broadly neutralizing and highly protective antibodies have grown in number, diversity, potency, and breadth of viral recognition and neutralization. These antibodies are now being further enhanced by rational engineering of their anti-HIV activities and coupled to cutting edge gene delivery and strategies to optimize their pharmacokinetics and biodistribution. As a result, the prospects for clinical use of HIV-specific antibodies to treat, clear, and prevent HIV infection are gaining momentum. Here we discuss the diverse methods whereby antibodies are being optimized for neutralization potency and breadth, biodistribution, pharmacokinetics, and effector function with the aim of revolutionizing HIV treatment and prevention options.

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Antibody Conjugation Approach Enhances Breadth and Potency of Neutralization of Anti-HIV-1 Antibodies and CD4-IgG

Cited by 20 publications

References 44 publications

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

Click Chemistry in Complex Mixtures: Bioorthogonal Bioconjugation

Antibody Conjugates: From Heterogeneous Populations to Defined Reagents

Engineering broadly neutralizing antibodies for HIV prevention and therapy

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