Site-selective protein conjugation at histidine

Peciak, Karolina; Laurine, Emmanuelle; Tommasi, Rita; Choi, Ji-Won; Brocchini, Steve

doi:10.1039/c8sc03355b

Cited by 46 publications

(38 citation statements)

References 115 publications

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“…Technologies for half-life extension are based on genetic engineering and post-translational modification of the biomolecule (e.g., bioconjugation and glycosylation) [ 54 ]. Increasingly it is becoming apparent that protein engineering and formulation can work hand in hand to increase the duration of drug action [ 55 ]. Increased stability and circulation times can sometimes be achieved, especially for peptides to degradation to peptidases by amino acid substitution to remove endopeptidase sites (e.g., exenatide) or to utilise D-amino acids (e.g., octreotide).…”

Section: General Strategies To Increase Duration Of Actionmentioning

confidence: 99%

“…The covalent conjugation of the water-soluble polymer poly(ethylene glycol) (PEG) to a therapeutic polypeptide can markedly increase circulation time by a range of mechanisms including (i) decreasing renal clearance rates due to the increased size of the conjugate and (ii) inhibiting enzymatic-mediated degradation and endocytic clearance due to PEG steric shielding. There is often a reduction in protein biological efficacy due to PEG steric shielding, which can be mitigated by site selective conjugation [ 55 ]. PEGylation is a clinically proven approach to improve the efficacy of many therapeutic proteins and enzymes, and several PEGylated products (including biosimilars) have become first-line treatments [ 69 ] with many PEGylated products continuing to be developed.…”

Section: General Strategies To Increase Duration Of Actionmentioning

confidence: 99%

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Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

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Proteins and peptides have emerged in recent years to treat a wide range of multifaceted diseases such as cancer, diabetes and inflammation. The emergence of polypeptides has yielded advancements in the fields of biopharmaceutical production and formulation. Polypeptides often display poor pharmacokinetics, limited permeability across biological barriers, suboptimal biodistribution, and some proclivity for immunogenicity. Frequent administration of polypeptides is generally required to maintain adequate therapeutic levels, which can limit efficacy and compliance while increasing adverse reactions. Many strategies to increase the duration of action of therapeutic polypeptides have been described with many clinical products having been developed. This review describes approaches to optimise polypeptide delivery organised by the commonly used routes of administration. Future innovations in formulation may hold the key to the continued successful development of proteins and peptides with optimal clinical properties.

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Section: General Strategies To Increase Duration Of Actionmentioning

confidence: 99%

Section: General Strategies To Increase Duration Of Actionmentioning

confidence: 99%

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

et al. 2020

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“…Recently, Brocchini and co-workers demonstrated that a His-Gly-His tag could be conveniently modified with a bis-sulfone reagent to site-specifically alkylate various positions of interferon (IFN) with a 10 kDa PEG chain ( Figure 6, panel B). [89] In another recent example, Bertozzi and co-workers reported the computational-guided discovery of an 11-amino acid tag (GGHPDPCPKGG) that undergoes a S-to-N transfer reaction to covalently modify Lys with a 2-cyanobenzothiazole reagent ( Figure 6, panel C). [90] The conformation of this peptide tag is engineered to place the Cys and Lys residues in proximity, promoting the intramolecular transfer in a mechanism similar to native chemical ligation.…”

Section: Covalent Labeling Via Tag-induced Reactivitymentioning

confidence: 99%

Proximity‐driven, Regioselective Chemical Modification of Peptides and Proteins

Hymel

Liu²

2020

Asian J Org Chem

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Chemical methods to covalently modify recombinant peptides and proteins are becoming increasingly valuable as the development of biological therapeutics accelerates. Rapid advances in chemoselectivity have been achieved to modify desired proteogenic and non-proteogenic amino acids. However, regioselectivity, in which a specific amino acid can be modified in the presence of chemically identical residues, has been much more difficult to achieve. This mini-review focuses on recent advances in regioselective chemical modification of peptides and proteins utilizing microenvironment and/or proximity-driven effects to achieve selectivity. While the chemistries and applications involving enzyme active site modification are still being steadily developed, such a concept has also been expanded to the modification of residues

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“…The heterogeneity of the conjugates formed in a labeling reaction is especially important, since heterogeneous conjugates are composed of a protein modified differently with respect to conjugation site and the number of labels leading to distinct behaviors for each species. For antibody drug conjugates, these differences have been associated with variations in pharmacokinetics and, in general, essential residues may be modified which might impair activity . Conjugation methods forming heterogeneous conjugates generally rely on excellent electrophiles, which react with abundant nucleophilic residues, such as lysines, on the surface of the protein.…”

Section: Introductionmentioning

confidence: 99%

Considerations on Probe Design for Affinity‐Guided Protein Conjugation

2019

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The plethora of methods developed for the creation of protein conjugates often differs significantly with regard to the heterogeneity of the resulting products, in the degree of genetic manipulation of the protein required, and in the technical skills required to perform the conjugation procedure. Affinity‐guided protein conjugation is a protein labeling methodology based on noncovalent binding interactions between a labeling probe and the protein of interest. These interactions increase the local concentration of a reactive group in the probe on the protein surface thus facilitating the conjugation in proximity of the complexation site. The ability to produce high‐quality conjugates from nongenetically modified proteins both in vitro, but also in cells, demonstrates the power of affinity‐guided protein conjugation. Here, we present the progress of affinity‐guided protein conjugation in relation to selective protein labeling in living systems and the formation of high‐quality protein conjugates. Furthermore, the probe design will be discussed in relation to the utility of the probe for labeling in vitro or in living systems.

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Site-selective protein conjugation at histidine

Abstract: Site-selective conjugation generally requires both (i) molecular engineering of the protein of interest to introduce a conjugation site at a defined location and (ii) a site-specific conjugation technology.

Cited by 46 publications

References 115 publications

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Injectables and Depots to Prolong Drug Action of Proteins and Peptides

Proximity‐driven, Regioselective Chemical Modification of Peptides and Proteins

Considerations on Probe Design for Affinity‐Guided Protein Conjugation

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