An efficient synthesis of argifin: a natural product chitinase inhibitor with chemotherapeutic potential.
The first synthesis of the cyclopentapeptide family 18 chitinase inhibitor argifin has been achieved by a combination of solid phase and solution chemistry. Synthetic argifin is a nanomolar inhibitor of chitinase B1 from Aspergillus fumigatus and the high-resolution X-ray structure of the synthesized material in complex with the same enzyme is identical to that previously obtained for the natural product.
Dixon
Mark J
MJ
Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Andersen
Ole A
OA
van Aalten
Daan M F
DM
Eggleston
Ian M
IM
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000201:enzymology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D002688:Chitinases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001688:Biological Products; D010456:Peptides, Cyclic; C413566:argifin; D002688:Chitinases