Macrocyclic peptides, including depsipeptides, are an emerging new modality in drug discovery research. Tetraselide, an antifungal cyclic peptide isolated from a marine-derived filamentous fungus, possesses a unique amphiphilic structural feature consisting of five consecutive β-hydroxy-amino acid residues and fatty acid moieties. Because the structure elucidation of the naturally occurring product left six stereocenters ambiguous, we implemented bioinformatic analyses, chemical degradation studies and chiral pool fragment synthesis to identify two of the undetermined stereocenters. Convergent total synthesis of the four remaining plausible isomers of tetraselide was accomplished liquid-phase peptide synthesis (LPPS) using soluble hydrophobic tag auxiliaries. The key advances involve fragment coupling by the serine/threonine ligation (STL) reaction and head-to-tail macrolactamization of the carrier-supported precursors that enabled systematic elaboration of the amphiphilic cyclic peptides. Ultimately, we determined the absolute structure of this natural product.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892018PMC
http://dx.doi.org/10.1039/d5sc00566cDOI Listing

Publication Analysis

Top Keywords

total synthesis
8
isolation total
4
synthesis
4
synthesis structure
4
structure determination
4
determination antifungal
4
antifungal macrocyclic
4
macrocyclic depsipeptide
4
depsipeptide tetraselide
4
tetraselide macrocyclic
4

Similar Publications

Background: Acceptance and commitment therapy provides a psychobehavioral framework feasible for digital and hybrid weight loss interventions. In face-to-face studies, group-based interventions yield more favorable outcomes than individual interventions, but the effect of the intervention form has not been studied in combination with eHealth.

Objective: This study investigated whether a minimal, 3-session group or individual enhancement could provide additional benefits compared to an eHealth-only intervention when assessing weight, body composition, and laboratory metrics in a sample of occupational health patients with obesity.

View Article and Find Full Text PDF

Glycerol dialkyl glycerol tetraethers (GDGTs) are a group of membrane spanning lipids produced by both Archaea and Bacteria. Branched GDGTs (brGDGTs) are a class of these tetraether lipids known to be produced by certain bacteria and are commonly found in terrestrial environments. Due to their environmental ubiquity, high preservation potential, and role in membrane adaptation, brGDGTs form the basis of many widely employed paleoenvironmental proxies.

View Article and Find Full Text PDF

Prostate cancer has garnered much importance in recent years due to its rising incidence and mortality among men worldwide. The ineffectiveness of existing therapies and adverse events associated with conventional treatment have led patients to turn towards traditional medicine for the management of prostate cancer. Cinnamomum zeylanicum bark essential oil (CZEO) possesses promising anticancer properties, yet the exact mechanism of action of CZEO for the management of prostate cancer remains unclear.

View Article and Find Full Text PDF

Introduction: Antimicrobial resistance (AMR) is one of the major global concerns in the current scenario. Mass-gathering events in fast-developing and densely populated areas may contribute to antibiotic resistance. Despite meticulous planning and infrastructure development, the effect of mass gatherings on microbial ecosystems and antibiotic resistance must be investigated.

View Article and Find Full Text PDF

Integrative single-cell and bulk RNA-seq analysis identifies lactylation-related signature in osteosarcoma.

Funct Integr Genomics

March 2025

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Osteosarcoma is the most common bone tumor and a highly aggressive malignant neoplasm. This study aims to elucidate the role of lactylation-related genes (LRGs) in osteosarcoma, with the goal of improving prognostic accuracy and enhancing the efficacy of immunotherapy. Using public datasets, we integrated differential and correlated genes based on single-cell sequencing AUCell scores and performed enrichment analysis and risk model construction on these genes.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!