Silver-promoted solid-phase guanidinylation enables the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue.

Cyclization and glycosylation serve as effective approaches for enhancing the drug properties of peptides. Distinct from typical glycosylation, atypical arginine N-glycosylation has drawn increasing attention due to its fundamental role in various cellular procedures and signaling pathways. We previously developed a robust strategy for constructing arginine N-glycosylated peptides characterized by silver-promoted solid-phase guanidinylation. Modeled after cyclic octapeptide Samoamide A, an antitumor peptide composed of eight hydrophobic amino acids extracted from cyanobacteria, herein we first performed arginine scanning to determine an optimal position for replacement with arginine. Consequently, the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue was described combining solid-phase glycosylation with solution-phase cyclization. The resultant SA-HH-TT displayed enhanced water solubility compared with the non-glycosylated SA-HH-TT. Notably, our method provides a universal strategy for synthesizing arginine N-glycosylated cyclopeptides.

Risk of bleeding in patients with continued dual antiplatelet therapy during orthopedic surgery.

BACKGROUND: To prevent risk of life-threatening stent thrombosis, all patients need to undergo dual antiplatelet therapy (DAPT) for at least 6 weeks to 12 months after stent implantation. If DAPT is continued during noncardiac surgery, there is a risk of severe bleeding at the surgical site. Our study was to assess the risk of bleeding in patients with continued DAPT during orthopedic surgery. METHODS: The clinical data of 78 patients with coronary heart disease who underwent orthopedic surgery from February 2006 to July 2018 were retrospectively analyzed. Prior to orthopedic surgery, DAPT was continued in 16 patients (group I), 24 patients were treated with single antiplatelet therapy (group II), and 26 patients received low-molecular-weight heparin therapy for more than 5 days after the discontinuation of all antiplatelet therapies (group III). Twelve patients were excluded, as they had undergone minimally invasive surgery such as transforaminal endoscopy and vertebroplasty. The perioperative blood loss of each patient was calculated using Nadler's formula and Gross' formula. The intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total blood loss were compared between groups. The level of significance was set at P < 0.05. RESULTS: There were no significant differences between the three groups in age, intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total perioperative blood loss calculated by Nadler's formula and Gross' formula (all P > 0.05). Six patients experienced postoperative cardiovascular complications due to the delayed restart of antiplatelet therapy; one of these patients in group III died from myocardial infarction. CONCLUSIONS: Continued DAPT or single antiplatelet treatment during orthopedic surgery does not increase the total intraoperative and perioperative bleeding compared with switching from antiplatelet therapy to low-molecular-weight heparin. However, the discontinuation of antiplatelet therapy increases the risk of serious cardiac complications.