Leveraging Hydrazide as Protection for Carboxylic Acid: Suppression of Aspartimide Formation during Fmoc Solid-Phase Peptide Synthesis.

Despite numerous optimizations in peptide synthesis, the formation of aspartimide remains a significant side reaction that needs to be addressed. Herein, we introduce an approach that utilizes hydrazide as a carboxylic-acid-protecting group to reduce the formation of aspartimide. The aspartic acid hydrazide effectively suppressed the formation of aspartimide, even under microwave conditions, and was readily converted to native aspartic acid using CuSO4 in an aqueous medium.

The small molecule STF-62247 induces apoptotic and autophagic cell death in leukemic cells.

Adult T cell leukemia/lymphoma (ATL) is an aggressive malignant T cell disease caused by human T cell leukemia virus-I (HTLV-1). Treatment outcomes for aggressive subtypes of ATL remain poor, with little improvement in overall survival since HTLV-1 was discovered. Therefore, new therapeutic strategies for ATL are required. STF-62247 induces autophagy and selectively kills renal cell carcinoma without apoptotic cell death. Here, we demonstrate that STF-62247 reduced cell viability and resulted in autophagosome accumulation and autophagy in leukemic cell lines (S1T, MT-2, and Jurkat). Interestingly, STF-62247 induced apoptosis in HTLV-1-infected cell lines (S1T and MT-2), as indicated by DNA fragmentation and caspase activation, but not in non-HTLV-1-infected Jurkat cells; a caspase inhibitor did not prevent this caspase-associated cell death. STF-62247 also increased nuclear endonuclease G levels. Furthermore, STF-62247 reduced cell viability and increased the number of apoptotic cells in peripheral blood mononuclear cells collected from patients with acute ATL, which has a poor prognosis. Therefore, STF-62247 may have novel therapeutic potential for ATL. This is the first evidence to demonstrate the cell growth-inhibitory effect of an autophagy inducer by caspase-dependent apoptosis and caspase-independent cell death via autophagy and endonuclease G in leukemic cells.

[Complete resolution of radiculopathy due to cervical vertebral artery dissection after intravascular treatment: a case report].

The authors report the case of a rare manifestation by vertebral artery dissection. A 15-year-old boy who presented with left shoulder weakness and numbness of the left arm was admitted to our hospital. Neurological examination on admission revealed muscle weakness of the left deltoid muscle and sensory disturbance of the left C5 area. MRI/MRA and 3D-CT angiography demonstrated an aneurysm-like dilatation of the left vertebral artery mainly at the C4/5 level. Partial thrombosis was noted in the dilated artery. The left vertebral angiogram showed that the second and third portions of the left vertebral artery had a dilated pseudo-lumen due to arterial dissection. The pseudo-lumen of the dissected vertebral artery was largest in diameter at the C4/5 level. The patient successfully underwent proximal occlusion of the dissected vertebral artery using detachable balloon and Guglielmi detachable coils. Proximal vertebral artery occlusion using an intravascular technique was regarded as a non-invasive and effective option for patients with a cervical radiculopathy due to cervical vertebral artery dissection.