In this study in patients with type 2 diabetes, near maximal glucose-lowering efficacy of sitagliptin after single oral doses was associated with inhibition of plasma DPP-4 activity of 80% or greater, corresponding to a plasma sitagliptin concentration of 100 nm or greater, and an augmentation of active GLP-1 and GIP levels of 2-fold or higher after an OGTT.

This review summarized the recent progress in the synthesis, characterization, properties, photoluminescence mechanism and biological applications of carbon dots.

The selection of DNA-encoded libraries against biological targets has become an important discovery method in chemical biology and drug discovery, but the requirement of modified and immobilized targets remains a significant disadvantage. With a terminal protection strategy and ligand-induced photo-crosslinking, we show that iterated selections of DNA-encoded libraries can be realized with unmodified and non-immobilized protein targets.

Background: ClpP1P2 is a novel protease complex essential for viability of Mycobacterium tuberculosis. Results: Cleavage preferences of ClpP1P2 were defined, which allowed us to design potent substrate-based boronate inhibitors showing anti-mycobacterial activity. Conclusion: Excellent new fluorogenic peptide substrates of ClpP1P2 were obtained, and novel enzyme properties were identified. Significance: Selective inhibition of ClpP1P2 activity is a promising approach for drug development.

The selectivity of an enzyme inhibitor is a key determinant of its usefulness as a tool compound or its safety as a drug. Yet selectivity is never assessed comprehensively in the early stages of the drug discovery process, and only rarely even in the later stages, because technical limitations prohibit doing otherwise. Here, we report EnPlex, an efficient, high-throughput method for simultaneously assessing inhibitor potency and specificity, and pilot its application to 96 serine hydrolases. EnPlex analysis of widely used serine hydrolase inhibitors revealed numerous previously unrecognized off-target interactions, some of which may help to explain previously confounding adverse effects. In addition, EnPlex screening of a hydrolase-directed library of boronic acid- and nitrile-containing compounds provided dual potency/selectivity structure-activity relationships from which lead candidates could be more effectively prioritized. Follow-up of a series of dipeptidyl peptidase 4 (DPP4) inhibitors showed that EnPlex indeed predicted efficacy and safety in animal models. These results demonstrate the feasibility and value of high-throughput, superfamily-wide selectivity profiling, and suggest such profiling can be incorporated into the earliest stages of drug discovery.

To address the requirements of biomedical applications including biosensing, bioimaging, and drug delivery, fluorescent nanomaterials served as efficient tools in many cases. Among them, near-infrared quantum dots (NIR QDs) have been used as novel fluorescent labels for their binary advantages of both QDs and NIR light. In this review, through collecting references in recent 10 years, we have introduced basic structures and properties of NIR QDs and summarized the classification and the related synthetic methods. This review also highlights the functionalization and surface bioconjugation of NIR QDs, and their biomedical applications in biosensing, bioimaging, and drug delivery. This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.

Near-infrared (NIR) quantum dots (QDs) have emerged as an attractive bioimaging toolkit for exploring biological events because they can provide deep imaging penetration and low fluorescence background. However, the quantitation process of such NIR QDs generally relies on single-emission intensity change, which is susceptible to a variety of environmental factors. Herein, for the first time, we proposed a protein-directed co-template strategy to synthesize a NIR-based, dual-emission fluorescent nanohybrid (DEFN) constructed from far-red gold nanoclusters and NIR PbS QDs (AuNCs-PbS-QDs). The convenient protein-directed co-template synthesis avoids the tedious chemical coupling and modification required in conventional preparation approaches of DEFNs. Additionally, the dual-emission signals of AuNCs-PbS-QDs exhibit two well-resolved emission peaks (640 and 813 nm) separated by 173 nm, which can eliminate environmental interferences by the built-in correction of ratiometric signal, resulting in a more favorable system for bioimaging and biosensing. Next, the target-responsive capability of this NIR-based DEFN to ascorbic acid (AA) was discovered, enabling the proposed DEFN to ratiometrically detect AA with a linear range of 3-40 μM and a detection limit of 1.5 μM. This DEFN sensor possesses high selectivity, rapid response, and excellent photostability. Moreover, the feasibility of this NIR nanosensor has been fully proved by the ratiometric detection of AA for fruit internal quality assessment, in vitro cellular imaging, and in vivo imaging in nude mice.

Nanozyme‐based chemodynamic therapy (CDT) has emerged as an effective cancer treatment because of its low side effects and without the requirement of exogenous energy. The therapeutic effect of CDT highlights the pivotal importance of active sites, H2O2 supplement and the glutathione (GSH) depletion of a nanozyme. The construction of a single kind of catalyst with multiple functions for the enhanced CDT is still a big challenge. In this work, seven types of bimetallic nanoparticles are synthesized using a metal–organic framework (MOF) as a stable host instead of a Fenton or Fenton‐like ions supplier. Among them, Cu‐Pd@MIL‐101 with an alloy loading of 9.5 wt% modified by PEG (9.5% CPMP) is found to exhibit the highest peroxidase (POD) like activity combined with a superoxide dismutase (SOD) mimic activity and the function of GSH depletion. The in vivo results suggest that the stable and ultrafine nanoparticles possess favorable CDT effect for tumor and good biosafety as well as biocompatibility. This work has provided a credible strategy to construct nanozymes with an excellent activity and may pave a new way for the design of enhanced tumor CDT treatment.