Unveiling a novel serpinB2-tripeptidyl peptidase II signaling axis during senescence.

Tripeptidyl peptidase II (TPPII or TPP2) degrades N-terminal tripeptides from proteins and peptides. Studies in both humans and mice have shown that TPPII deficiency is linked to cellular immune-senescence, lifespan regulation and the aging process. However, the mechanism of how TPPII participates in these processes is less clear.

Development of Activity-Based Probes for Imaging Human α-l-Fucosidases in Cells.

We have established a concise synthetic route relying on a key base-promoted epimerization step to synthesize two series of activity-based probes carrying a BODIPY fluorophore for α-l-fucosidase. The resulting probes were evaluated for labeling performance. The one utilizing an o-fluoromethylphenol derivative as the latent trapping unit was successfully applied for the first time to visualize and locate lysosomal α-l-fucosidase activity in human cells.

Development and evaluation of novel phosphotyrosine mimetic inhibitors targeting the Src homology 2 domain of signaling lymphocytic activation molecule (SLAM) associated protein.

Specific interactions between Src homology 2 (SH2) domain-containing proteins and the phosphotyrosine-containing counterparts play significant role in cellular protein tyrosine kinase (PTK) signaling pathways. The SH2 domain inhibitors could potentially serve as drug candidates in treating human diseases. Here we have incorporated a novel phosphotyrosine mimetic, which is an unusual amino acid carrying a cyclosaligenyl (cycloSal) phosphodiester moiety, into dipeptides to investigate the inhibitory effect on SH2 domain-containing proteins.

Fluorous oxime palladacycle: a precatalyst for carbon-carbon coupling reactions in aqueous and organic medium.

To facilitate precatalyst recovery and reuse, we have developed a fluorous, oxime-based palladacycle 1 and demonstrated that it is a very efficient and versatile precatalyst for a wide range of carbon-carbon bond formation reactions (Suzuki-Miyaura, Sonogashira, Stille, Heck, Glaser-type, and Kumada) in either aqueous or organic medium under microwave irradiation. Palladacycle 1 could be recovered through F-SPE in various coupling reactions with recovery ranging from 84 to 95% for the first cycle. Inductively coupled plasma optical emission spectrometry (ICP-OES) analyses of the Pd content in the crude product from each class of transformation indicated extremely low levels of leaching and the palladacycle could be reused four to five times without significant loss of activity.

Selective activation of SHP2 activity by cisplatin revealed by a novel chemical probe-based assay.

Src homology-2 (SH2) domain-containing phosphatase 2 (SHP2) is known to participate in several different signaling pathways to mediate cell growth, survival, migration, and differentiation. However, due to the lack of proper analytical tools, it is unclear whether the phosphatase activity of SHP2 is activated in most studies. We have previously developed an activity-based probe LCL2 that formed covalent linkage with catalytically active protein tyrosine phosphatases (PTPs).

Rapid and selective isolation of beta-xylosidase through an activity-based chemical approach.

beta-Xylosidase is a key enzyme in the xylanolytic system with a great potential in many biotechnological applications, especially in the food as well as the pulp and paper industries. We have developed a chemical approach for the rapid screening and isolation of beta-xylosidase. Activity probe LCL-6X targeting beta-xylosidase was utilized in this study.

Development of highly selective and sensitive probes for hydrogen.

Probes that react specifically with hydrogen peroxide to release chromophoric or fluorescent reporter groups were designed and synthesized.