Versatile and Efficient Site‐Specific Protein Functionalization by Tubulin Tyrosine Ligase

Schumacher, Dominik; Helma, Jonas; Mann, Florian A.; Pichler, Garwin; Natale, Francesco; Krause, Eberhard; Cardoso, M. Cristina; Hackenberger, Christian P. R.; Leonhardt, Heinrich

doi:10.1002/anie.201505456

Cited by 87 publications

(82 citation statements)

References 45 publications

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“…30 The docking studies of these derivatives showed that this reactivity can be traced back to three binding modes. For small substituents such as fluorine and chlorine that have a negative partial charge, the binding behavior is similar to that of tyrosine ( 4 ) and the substituent points towards the small positively charged pocket formed by arginine-202 and tryptophan-204 (ESI Fig.…”

Section: Resultsmentioning

confidence: 99%

Broad substrate tolerance of tubulin tyrosine ligase enables one-step site-specific enzymatic protein labeling

et al. 2017

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Section: Resultsmentioning

confidence: 99%

Broad substrate tolerance of tubulin tyrosine ligase enables one-step site-specific enzymatic protein labeling

et al. 2017

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“…Ligases have also been exploited to add new functionality to mAbs. These include Sortase, tubulin tyrosine ligase, and spyligase . In each case a specific peptide sequence is added to the C‐terminus of the light and/or heavy chains of the mAb.…”

Section: Resultsmentioning

confidence: 99%

Improving theranostics in pancreatic cancer

King

Bouvet

Singh

et al. 2017

Journal of Surgical Oncology

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Background Pancreatic cancer is the fourth most deadly cancer in the US, and is expected to be the second most deadly by 2030. The major difficulty in treating pancreatic cancer is the late onset of symptoms. Generally, patients show metastatic disease by the time of diagnosis, with a survival rate of 5% beyond 5 years. In patients without metastatic disease, surgical resection increases 5 year survival rate to 25%. The remaining 75% succumb to undetected metastases. Clearly, improvements to both detection, surgical intervention, and therapeutic strategies will be needed to improve patient outcome in pancreatic cancer. Methods Recent literature has been surveyed and atomic models of new therapeutic appoaches were generated. Results and Conclusions Here, we focus on the recent progress employing monoclonal antibodies (mAbs) to target pancreatic cancer associated markers, and more specifically on recent chemical and protein engineering efforts to improve the homogeneity, stability, and administration of mAbs to precisely delivery imaging agents and cytotoxins to sites of disease.

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“…Popular approaches to achieve this goal include chemo‐enzymatic tag‐based functionalization methods that combine enzyme‐specific protein tags and labeling probes that are enzymatically transferred to the appropriate tag . Examples of these strategies include biotin ligase (BirA), spy ligase, formylglycine‐generating enzyme (FGE), sortase A (SrtA), transglutaminase, phosphopantetheinyl transferases Sfp and AcpS, and tubulin tyrosine ligase . However, the specificities of the exploited enzymes for their corresponding recognition tags are often accompanied by a rather narrow tolerance for suitably derivatized labeling probes.…”

Section: Methodsmentioning

confidence: 99%

Exploring the Substrate Scope of the Bacterial Phosphocholine Transferase AnkX for Versatile Protein Functionalization

2019

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Site‐specific protein functionalization has become an indispensable tool in modern life sciences. Here, tag‐based enzymatic protein functionalization techniques are among the most versatilely applicable approaches. However, many chemo‐enzymatic functionalization strategies suffer from low substrate scopes of the enzymes utilized for functional labeling probes. We report on the wide substrate scope of the bacterial enzyme AnkX towards derivatized CDP‐choline analogues and demonstrate that AnkX‐catalyzed phosphocholination can be used for site‐specific one‐ and two‐step protein labeling with a broad array of different functionalities, displaying fast second‐order transfer rates of 5×102 to 1.8×104 m−1 s−1. Furthermore, we also present a strategy for the site‐specific dual labeling of proteins of interest, based on the exploitation of AnkX and the delabeling function of the enzyme Lem3. Our results contribute to the wide field of protein functionalization, offering an attractive chemo‐enzymatic tag‐based modification strategy for in vitro labeling.

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Versatile and Efficient Site‐Specific Protein Functionalization by Tubulin Tyrosine Ligase

Cited by 87 publications

References 45 publications

Broad substrate tolerance of tubulin tyrosine ligase enables one-step site-specific enzymatic protein labeling

Broad substrate tolerance of tubulin tyrosine ligase enables one-step site-specific enzymatic protein labeling

Improving theranostics in pancreatic cancer

Exploring the Substrate Scope of the Bacterial Phosphocholine Transferase AnkX for Versatile Protein Functionalization

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