A light-responsive, self-immolative linker for controlled drug delivery <i>via</i> peptide- and protein-drug conjugates

Zang, Chuanlong; Wang, Huawei; Li, Tiantian; Zhang, Y; Li, Jiahui; Shang, Mengdi; Du, Juanjuan; Xi, Zhen; Zhou, Chuanzheng

doi:10.1039/c9sc03016f

Cited by 32 publications

(27 citation statements)

References 44 publications

(53 reference statements)

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“…Preparation of 3Br-5MPs. 3Br-5MPs were first synthesized by means of the same strategy used for 5MPs 10,35 . Specifically, a variety of primary amine substrates (2a-g) were coupled with intermediate 1′ in neutral aqueous solution to furnish the corresponding 3Br-5MPs (3a-g) in modest yields (Method 1 in Table 1).…”

Section: Resultsmentioning

confidence: 99%

Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones

Zhang

Zang

et al. 2020

Nat Commun

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Many reagents have been developed for cysteine-specific protein modification. However, few of them allow for multi-functionalization of a single Cys residue and disulfide bridging bioconjugation. Herein, we report 3-bromo-5-methylene pyrrolones (3Br-5MPs) as a simple, robust, and versatile class of reagents for cysteine-specific protein modification. These compounds can be facilely synthesized via a one-pot mild reaction and they show comparable tagging efficiency but higher cysteine specificity than the maleimide counterparts. The addition of cysteine to 3Br-5MPs generates conjugates that are amenable to secondary addition by another thiol or cysteine, making 3Br-5MPs valuable for multi-functionalization of a single cysteine and disulfide bridging bioconjugation. The labeling reaction and subsequent treatments are mild enough to produce stable and active protein conjugates for biological applications.

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Section: Resultsmentioning

confidence: 99%

Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones

Zhang

Zang

et al. 2020

Nat Commun

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“…Photodecaging led to rapid DOX release via the addition–elimination cascade, enabled targeted, controlled drug delivery. [ 39 ]…”

Section: Photochemically Triggered Drug Deliverymentioning

confidence: 99%

Light: A Magical Tool for Controlled Drug Delivery

Tao

Chan

Shi

et al. 2020

Adv Funct Materials

165

141

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Light is a particularly appealing tool for on-demand drug delivery due to its noninvasive nature, ease of application, and exquisite temporal and spatial control. Great progress is achieved in the development of novel light-driven drug delivery strategies with both breadth and depth. Light-controlled drug delivery platforms can be generally categorized into three groups: photochemical, photothermal, and photoisomerization-mediated therapies. Various advanced materials, such as metal nanoparticles, metal sulfides and oxides, metal-organic frameworks, carbon nanomaterials, upconversion nanoparticles, semiconductor nanoparticles, stimuli-responsive micelles, polymer-and liposome-based nanoparticles are applied for light-stimulated drug delivery. In view of the increasing interest in on-demand targeted drug delivery, the development of light-responsive systems with a focus on recent advances, key limitations, and future directions is reviewed.

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“…However, there are also more complex linkers that release the drug in response to external stimuli such as temperature, magnetic field, ultrasound or light [ 76 ]. As an example, Zang et al designed a new light-responsive self-immolative linker, namely PC4AP, for DOX conjugation to the H3 mutant H3-V35C CPP [ 26 ]. This linker was a derivate of deoxyribose with the C4 and C hydroxyl groups O -nitrobenzyl protected.…”

Section: Cpp–drug Conjugation Using Functionalized Linkersmentioning

confidence: 99%

Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques

2021

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This review summarizes recent developments in conjugation techniques for the synthesis of cell-penetrating peptide (CPP)–drug conjugates targeting cancer cells. We will focus on small organic molecules as well as metal complexes that were used as cytostatic payloads. Moreover, two principle ways of coupling chemistry will be discussed direct conjugation as well as the use of bifunctional linkers. While direct conjugation of the drug to the CPP is still popular, the use of bifunctional linkers seems to gain increasing attention as it offers more advantages related to the linker chemistry. Thus, three main categories of linkers will be highlighted, forming either disulfide acid-sensitive or stimuli-sensitive bonds. All techniques will be thoroughly discussed by their pros and cons with the aim to help the reader in the choice of the optimal conjugation technique that might be used for the synthesis of a given CPP–drug conjugate

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A light-responsive, self-immolative linker for controlled drug delivery via peptide- and protein-drug conjugates

Abstract: Photoirradiation of the PC4AP linker generates an active intermediate that reacts intramolecularly with a primary amine on the carrier peptide/protein, leading to rapid release of the drug without generating any toxic side products.

Cited by 32 publications

References 44 publications

Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones

Cysteine-specific protein multi-functionalization and disulfide bridging using 3-bromo-5-methylene pyrrolones

Light: A Magical Tool for Controlled Drug Delivery

Recent Advances and Trends in Chemical CPP–Drug Conjugation Techniques

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