Dual modification of biomolecules

Maruani, Antoine; Richards, Daniel A.; Chudasama, Vijay

doi:10.1039/c6ob01010e

Cited by 53 publications

(55 citation statements)

References 95 publications

(155 reference statements)

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“…A number of other approaches for the site‐specific conjugation of two separate agents to an antibody have been presented (recently reviewed in Ref. 11), but most of these methods require specialized reagents including site‐specific amino acid mutations or custom enzymes, and sometimes require two distinct conjugation handles. All of these factors increase the complexity of reagents required to generate and screen multi‐drug ADCs.…”

mentioning

confidence: 99%

Orthogonal Cysteine Protection Enables Homogeneous Multi‐Drug Antibody–Drug Conjugates

et al. 2016

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A strategy for the preparation of homogeneous antibody–drug conjugates (ADCs) containing multiple payloads has been developed. This approach utilizes sequential unmasking of cysteine residues with orthogonal protection to enable site‐specific conjugation of each drug. In addition, because the approach utilizes conjugation to native antibody cysteine residues, it is widely applicable and enables high drug loading for improved ADC potency. To highlight the benefits of ADC dual drug delivery, this strategy was applied to the preparation of ADCs containing two classes of auristatin drug‐linkers that have differing physiochemical properties and exert complementary anti‐cancer activities. Dual‐auristatin ADCs imparted activity in cell line and xenograft models that are refractory to ADCs comprised of the individual auristatin components. This work presents a facile method for construction of potent dual‐drug ADCs and demonstrates how delivery of multiple cytotoxic warheads can lead to improved ADC activities. Lastly, we anticipate that the conditions utilized herein for orthogonal cysteine unmasking are not restricted to ADCs and can be broadly utilized for site‐specific protein modification.

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confidence: 99%

Orthogonal Cysteine Protection Enables Homogeneous Multi‐Drug Antibody–Drug Conjugates

et al. 2016

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“…Particularly, playing with substituents present in biomolecules are of great interest as they triggered several bio‐chemical events in the living systems . Interestingly, suitably modified biomolecules have demonstrated several interesting material properties . They have recently drawn significant attention in bio‐optoelectronics as they can be more environment friendly due to their low toxicity, potential for easy waste disposal and biodegradability.…”

Section: Introductionmentioning

confidence: 99%

“…[2,3] Interestingly, suitably modified biomolecules have demonstrated several interesting material properties. [4][5][6][7] They have recently drawn significant attention in biooptoelectronics [8] as they can be more environment friendly due to their low toxicity, potential for easy waste disposal [9] and biodegradability. [9][10][11][12] Further, bio-derived small molecules upon subtle modifications in the structures have been introduced as an efficient candidate in the realm of organic electronics.…”

Section: Introductionmentioning

confidence: 99%

Tuning Thin Film Properties by Structural Modulations in Red Fluorescent Protein Chromophore Analogues

et al. 2019

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The study of the role of substituents present in molecules is extremely important for designing new functional materials. In the present study, we have designed and synthesized four analogues (AR1‐AR4) of the red fluorescence protein (rfp) chromophore by varying the substituents and have studied their thin film properties by fabricating opto‐electronic devices with them. Molecules AR1 and AR2 were designed with improved donor‐acceptor (D−A) properties. Molecule AR3 was synthesized with an increased vinyl conjugation and molecule AR4 had an extra fluorescent moiety in the conjugation. The orbital levels and optical energy gap were estimated theoretically by density function theory. The optical absorption in solution/thin films, quality of film formation and the electrical charge transport mobility in films were studied. Photovoltaic parameters of bulk heterojunction solar cell devices formed with the four molecules were then determined. Interestingly, molecule AR3 with the extra vinyl conjugation was found to be the best of the four molecules reported here for application in organic electronics. The extra vinyl conjugation improved the π‐π stacking and helps to form smoother films with increased optical absorption and a desirable hole mobility.

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“…As an additional benefit, we anticipated the β-hydroxy aldehyde product of the cross aldol reaction could be subjected to alternative aldehyde ligation conditions to afford dual modified proteins, which are of increasing utility. 32 Herein we disclose the realisation of this strategy in an ‘organocatalyst-mediated protein aldol ligation’ (OPAL) that enables site-selective formation of stable C–C bonds to protein aldehydes 2 at neutral pH at internal sites within folded proteins, and at the N-terminus ( Fig. 1 , enamine activation mode).…”

Section: Introductionmentioning

confidence: 99%

Site-selective C–C modification of proteins at neutral pH using organocatalyst-mediated cross aldol ligations

et al. 2018

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Dual modification of biomolecules

Abstract: Fromde novoapproaches on oligonucleotides to the post-translational functionalisation of proteins, this review will highlight the main strategies to dually modify biological entities.

Cited by 53 publications

References 95 publications

Orthogonal Cysteine Protection Enables Homogeneous Multi‐Drug Antibody–Drug Conjugates

Orthogonal Cysteine Protection Enables Homogeneous Multi‐Drug Antibody–Drug Conjugates

Tuning Thin Film Properties by Structural Modulations in Red Fluorescent Protein Chromophore Analogues

Site-selective C–C modification of proteins at neutral pH using organocatalyst-mediated cross aldol ligations

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