New Generation of Specific Trypanosoma cruzi trans-Sialidase Inhibitors

• Published in: Angewandte Chemie (International ed.) Vol. 47; no. 14; pp. 2700 - 2703
• Main Authors: Buchini, Sabrina, Buschiazzo, Alejandro, Withers, Stephen G
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 25.03.2008; WILEY-VCH Verlag; WILEY‐VCH Verlag
• Subjects: Animals; Biochemistry; Biochemistry, Molecular Biology; bioorganic chemistry; Chemical Sciences; Cristallography; Crystallography, X-Ray; enzymes; Glycoproteins; Glycoproteins - antagonists & inhibitors; Glycoproteins - chemistry; Glycoproteins - metabolism; inhibitors; Kinetics; Life Sciences; Models, Molecular; Molecular Structure; Neuraminidase; Neuraminidase - antagonists & inhibitors; Neuraminidase - chemistry; Neuraminidase - metabolism; Protease Inhibitors; Protease Inhibitors - chemical synthesis; Protease Inhibitors - chemistry; Protease Inhibitors - pharmacology; Sensitivity and Specificity; structure elucidation; Trypanosoma cruzi; Trypanosoma cruzi - enzymology
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.200705435

A substitution for inhibition: The incorporation of an aryl substituent at C9 of 3‐fluorosialyl fluorides provides specificity and dramatically slows the reactivation of the glycosylphosphatidylinositol‐anchored surface protein Trypanosoma cruzi trans‐sialidase (TcTS) by transglycosylation (see picture). X‐ray crystallographic analysis of the trapped intermediate has provided a structural rationale for this behavior.