Chemical modification of proteins – challenges and trends at the start of the 2020s

Fischer, Niklas Henrik; Oliveira, Maria Teresa; Diness, Frederik

doi:10.1039/d2bm01237e

Cited by 26 publications

(13 citation statements)

References 275 publications

(461 reference statements)

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“…The chemical modification of biotherapeutics, and proteins in particular, is often complicated by a loss of biomolecule functionality subsequent to modification . We therefore examined the effect of our bioconjugation strategy on the activity of cytokines, which are moderately sized cell-signaling proteins often leveraged in immune modulation to treat cancer, autoimmune disorders, and infectious diseases .…”

Section: Resultsmentioning

confidence: 99%

Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery

D’Elia,

Jones,

Canziani

et al. 2024

ACS Biomater. Sci. Eng.

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Protein therapeutics represent a rapidly growing class of pharmaceutical agents that hold great promise for the treatment of various diseases such as cancer and autoimmune dysfunction. Conventional systemic delivery approaches, however, result in off-target drug exposure and a short therapeutic half-life, highlighting the need for more localized and controlled delivery. We have developed an affinity-based protein delivery system that uses guest−host complexation between β-cyclodextrin (CD, host) and adamantane (Ad, guest) to enable sustained localized biomolecule presentation. Hydrogels were formed by the copolymerization of methacrylated CD and methacrylated dextran. Extrusion fragmentation of bulk hydrogels yielded shear-thinning and self-healing granular hydrogels (particle diameter = 32.4 ± 16.4 μm) suitable for minimally invasive delivery and with a high host capacity for the retention of guest-modified proteins. Bovine serum albumin (BSA) was controllably conjugated to Ad via EDC chemistry without affecting the affinity of the Ad moiety for CD (K D = 12.0 ± 1.81 μM; isothermal titration calorimetry). The avidity of Ad−BSA conjugates was directly tunable through the number of guest groups attached, resulting in a fourfold increase in the complex half-life (t 1/2 = 5.07 ± 1.23 h, surface plasmon resonance) that enabled a fivefold reduction in protein release at 28 days. Furthermore, we demonstrated that the conjugation of Ad to immunomodulatory cytokines (IL-4, IL-10, and IFNγ) did not detrimentally affect cytokine bioactivity and enabled their sustained release. Our strategy of avidity-controlled delivery of proteinbased therapeutics is a promising approach for the sustained local presentation of protein therapeutics and can be applied to numerous biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery

D’Elia,

Jones,

Canziani

et al. 2024

ACS Biomater. Sci. Eng.

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“…189 Since the incorporation of unnatural amino acids into proteins or larger peptides has become more accessible by genetic code expansion or site-specific modification, the elucidation of protein-based host-pathogen interaction is now more easily accessible. [190][191][192][193][194][195] Studying macromolecule-based communication could greatly benefit from chemical proteomics and would further eludicate another aspect of host-pathogen interactions from both bacterial and host perspectives. 196 The antimicrobial resistance crisis requires novel approaches to treating bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Monitoring host–pathogen interactions using chemical proteomics

Weigert Muñoz,

Zhao,

Sieber

2024

RSC Chem. Biol.

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“…389,390 The imidazole portion of His is subject to oxidation through several mechanisms, including the action of peroxides, singlet oxygen, metal catalysis, as well as of other photoinduced processes. 391 The oxidation of His by singlet oxygen generates peroxides whose decomposition leads to several products, including 5-hydroxy-5-alkyl-1,5-dihydro-2H-imidazol-2-one, which can be attacked by amino acids possessing nucleophilic side chains such as His, Lys, Arg, and Cys to form potentially photoactive compounds. Copolymers of N-(2-hydroxypropyl) methacrylamide containing His and Lys and ribonuclease A submitted to light irradiation show His-His and His-Lys bonds whose formation involves imidazol-2-one intermediates.…”

Section: Chemical Reviewsmentioning

confidence: 99%

Endogenous Photosensitizers in Human Skin

2023

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Endogenous photosensitizers play a critical role in both beneficial and harmful light-induced transformations in biological systems. Understanding their mode of action is essential for advancing fields such as photomedicine, photoredox catalysis, environmental science, and the development of sun care products. This review offers a comprehensive analysis of endogenous photosensitizers in human skin, investigating the connections between their electronic excitation and the subsequent activation or damage of organic biomolecules. We gather the physicochemical and photochemical properties of key endogenous photosensitizers and examine the relationships between their chemical reactivity, location within the skin, and the primary biochemical events following solar radiation exposure, along with their influence on skin physiology and pathology. An important take-home message of this review is that photosensitization allows visible light and UV-A radiation to have large effects on skin. The analysis presented here unveils potential causes for the continuous increase in global skin cancer cases and emphasizes the limitations of current sun protection approaches.

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Chemical modification of proteins – challenges and trends at the start of the 2020s

Abstract: Ribosomally expressed proteins perform multiple, versatile, and specialized tasks throughout Nature. In modern times, chemically modified proteins, including improved hormones, enzymes, and antibody-drug-conjugates have become available and have found advanced...

Cited by 26 publications

References 275 publications

Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery

Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery

Monitoring host–pathogen interactions using chemical proteomics

Endogenous Photosensitizers in Human Skin

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