Thiazolidine chemistry revisited: a fast, efficient and stable click-type reaction at physiological pH

Bermejo-Velasco, Daniel; Nawale, Ganesh N.; Oommen, Oommen P.; Hilborn, Jöns; Varghese, Oommen P.

doi:10.1039/c8cc05405c

Cited by 37 publications

(46 citation statements)

References 43 publications

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“…Since most of the residues involved in the recognition of the THF AP site and thiazolidine linkage are strictly conserved among bacteria, yeast, plants, and animals (Supplementary Figure S2A), the mechanism deduced from our studies can be extended to other SRAP domain-containing proteins and human HMCES. The stable chemical nature of the thiazolidine linkage (28) correlates well with the way HMCES effectively shields ssDNA AP sites from AP endonucleases and translesion DNA synthesis (TLS) polymerases, thus protecting genome integrity by promoting error-free AP site repair (12).…”

Section: Discussionmentioning

confidence: 99%

Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK

Wang

Bao

Chen

et al. 2019

Nucleic Acids Research

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HMCES and yedK were recently identified as sensors of abasic sites in ssDNA. In this study, we present multiple crystal structures captured in the apo-, nonspecific-substrate-binding, specific-substrate-binding, and product-binding states of yedK. In combination with biochemical data, we unveil the molecular basis of AP site sensing in ssDNA by yedK. Our results indicate that yedK has a strong preference for AP site-containing ssDNA over native ssDNA and that the conserved Glu105 residue is important for identifying AP sites in ssDNA. Moreover, our results reveal that a thiazolidine linkage is formed between yedK and AP sites in ssDNA, with the residues that stabilize the thiazolidine linkage important for the formation of DNA-protein crosslinks between yedK and the AP sites. We propose that our findings offer a unique platform to develop yedK and other SRAP domain-containing proteins as tools for detecting abasic sites in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK

Wang

Bao

Chen

et al. 2019

Nucleic Acids Research

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“…The thiazolidine ligation reaction between a 1,2‐aminothiol and an aldehyde proceeds rapidly under physiological pH and temperature, yielding a thiazolidine linkage, which is stable at acidic and neutral pH. [ 255 ] In 2004, Grinstaff and colleagues reported the use of this reaction to fabricate hydrogels using a dendritic peptide with multiple N ‐terminal cysteine moieties, coined as a biodendrimer, and a PEG dialdehyde ( Figure ). [ 146 ] The gelation time is less than three minutes and the resulting hydrogels have a refractive index similar to that of human cornea.…”

Section: Crosslinking Chemistrymentioning

confidence: 99%

Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact

2021

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Hydrogels are an important class of biomaterials with the unique property of high‐water content in a crosslinked polymer network. In particular, chemically crosslinked hydrogels have made a great clinical impact in past years because of their desirable mechanical properties and tunability of structural and chemical properties. Various polymers and step‐growth crosslinking chemistries are harnessed for fabricating such covalently crosslinked hydrogels for translational research. However, selecting appropriate crosslinking chemistries and polymers for the intended clinical application is time‐consuming and challenging. It requires the integration of polymer chemistry knowledge with thoughtful crosslinking reaction design. This task becomes even more challenging when other factors such as the biological mechanisms of the pathology, practical administration routes, and regulatory requirements add additional constraints. In this review, key features of crosslinking chemistries and polymers commonly used for preparing translatable hydrogels are outlined and their performance in biological systems is summarized. The examples of effective polymer/crosslinking chemistry combinations that have yielded clinically approved hydrogel products are specifically highlighted. These hydrogel design parameters in the context of the regulatory process and clinical translation barriers, providing a guideline for the rational selection of polymer/crosslinking chemistry combinations to construct hydrogels with high translational potential are further considered.

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“…[37] Bermejo-Velasco et al recently published a method to tackle the electron deficiency problem. [41] In this work, instead of using aryl aldehyde, aliphatic aldehyde (propionaldehyde) was employed to target both free cysteine and peptides containing N-terminal cysteine.…”

Section: Aldehyde Derivatives Via Thiazolidine Formationmentioning

confidence: 99%

“…To date, several electrophilic chemical groups have been developed that target this binucleophilic group, leading to the formation of a relatively stable thiazolidine ring via reductive alkylation of the amino group (resulting in the formation of an iminium ion [39,40] ) and the intramolecular addition of the cysteinyl thiol group to the iminium ion. [41] In this review, we focus on different chemical approaches and reaction conditions for the N-terminal cysteine modification in proteins.…”

Section: Introductionmentioning

confidence: 99%

Recent advances in protein modifications techniques for the targeting N‐terminal cysteine

Nicholas

Mazid

Murale³

et al. 2021

Peptide Science

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N-terminal modifications of proteins have garnered the attention of chemical biologists because of their critical roles in numerous cellular processes, including protein translocation, protein structural and metabolic stability, and the regulation of the half-life of proteins by a process known as "N-end rule pathway." In addition, other posttranslational modification processes also depend on the N-terminal signal sequences. Chemical probes are powerful tools that can be used to investigate N-terminal modifications, to gain structural and functional insights into protein modification, protein-protein interactions, protein localization, and protein dynamics. Most modifications target cysteine and lysine residues because of their high nucleophilicity. However, due to multiple occurrences of these residues in a protein at a given time, regioselective labeling can be quite difficult to accomplish. N-terminal cysteine presents itself as a unique practical option to overcome regioselectivity and site-specificity challenges. This review provides an overview of N-terminal cysteine labeling tools, including N-terminal cysteine condensation with aldehydes, cyanobenzothiazoles, cyclopropenones, and trans-thioesterification. The review also highlights the technical challenges of each of the techniques, which need to be addressed to broaden the scope of these approaches.

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Thiazolidine chemistry revisited: a fast, efficient and stable click-type reaction at physiological pH

Abstract: We describe the fast reaction kinetics between 1,2-aminothiols and aldehydes that afforded a stable thiazolidine product under physiological pH. This efficient and biocompatible reaction offers enormous potential for the coupling of biomolecules.

Cited by 37 publications

References 43 publications

Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK

Molecular basis of abasic site sensing in single-stranded DNA by the SRAP domain of E. coli yedK

Covalently Crosslinked Hydrogels via Step‐Growth Reactions: Crosslinking Chemistries, Polymers, and Clinical Impact

Recent advances in protein modifications techniques for the targeting N‐terminal cysteine

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