Novel design of potent anti-tumour activity of IL-2 prodrug by FAPα-mediated activation.

Interleukin-2 (IL-2) is a T cell growth factor that is essential for the proliferation of T cells and the generation of effector and memory cells. The antitumor activity of high-dose IL-2 therapy requires maintaining the affinity between IL-2 and IL2-Rα, which can also bring serious toxic side effects. To address this issue, we designed ZGP-Cysteamine-IL-2-K64C and (ZGP-Cysteamine)-IL-2-(K43C, K64C) based on the strategy of FAPα enzyme-activated prodrugs, and investigated their anti-tumour activity and side effects.

A two-step method preparation of semaglutide through solid-phase synthesis and inclusion body expression.

Semaglutide is currently the most promising antidiabetic drug, especially for the treatment of type 2 diabetes mellitus, due to its excellent efficacy in glycemic control and weight loss. However, the production of semaglutide remains high cost, and high yield, low cost, and high purity still remains a challenge. Herein, we reported a convenient and high-yield strategy for the preparation of semaglutide through fragmented condensation coupling, involving solid-phase peptide synthesis of tetrapeptide and on-column refolding and on-column enzyme cleavage based inclusion body expression of LysArgGLP-1 (11-37) with fused protein tags in an X-Y-D4K-G pattern.

Engineering of highly potent and selective HNTX-III mutant against hNa1.7 sodium channel for treatment of pain.

Human voltage-gated sodium channel Na1.7 (hNa1.7) is involved in the generation and conduction of neuropathic and nociceptive pain signals.

Sepiapterin reductase promotes hepatocellular carcinoma progression via FoxO3a/Bim signaling in a nonenzymatic manner.

Sepiapterin reductase plays an enzymatic role in the biosynthesis of tetrahydrobiopterin, which is reported in limited studies to regulate the progression of several tumors. However, the role of sepiapterin reductase in hepatocellular carcinoma remains largely unknown. Here, we found that sepiapterin reductase was frequently highly expressed in human hepatocellular carcinoma, which was significantly associated with higher T stage, higher tumor node metastasis stage, and even shorter survival of hepatocellular carcinoma patients.

Discovery of a Novel Na1.7 Inhibitor From Venom With Potent Analgesic Efficacy.

Spider venoms contain a vast array of bioactive peptides targeting ion channels. A large number of peptides have high potency and selectivity toward sodium channels. Na1.

µ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects.

Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.

Engineering Gain-of-Function Analogues of the Spider Venom Peptide HNTX-I, A Potent Blocker of the hNa1.7 Sodium Channel.

Pain is a medical condition that interferes with normal human life and work and reduces human well-being worldwide. The voltage-gated sodium channel (VGSC) human Na1.7 (hNa1.

The peptide toxin δ-hexatoxin-MrIX inhibits fast inactivation of Nas in mouse cerebellar granule cells.

Spider venom is rich in peptide toxins that could be used to explore the structure and function of voltage-gated sodium channels (Nas). This study has characterized a 44-amino acid peptide toxin, δ-hexatoxin-MrIX (δ-HXTX-MrIX), from the venom of the spider Macrothele raveni. δ-hexatoxin-MrIX potently inhibited the fast inactivation of Nas in mouse cerebellar granule cells (CGCs) with an EC of 35.

Synthesis and analgesic effects of μ-TRTX-Hhn1b on models of inflammatory and neuropathic pain.

μ-TRTX-Hhn1b (HNTX-IV) is a 35-amino acid peptide isolated from the venom of the spider, Ornithoctonus hainana. It inhibits voltage-gated sodium channel Nav1.7, which has been considered as a therapeutic target for pain.