Antifungal activity of a Candida albicans GGTase I inhibitor-alanine conjugate. Inhibition of Rho1p prenylation in C. albicans.
An alanine conjugate of a Candida albicans geranylgeranyl transferase I inhibitor was synthesized to facilitate its uptake into the fungal cell. The antifungal activity of CaGGTase-Ala conjugate is demonstrated. It is also shown that the CaGGTase-Ala conjugate affects prenylation of endogenous Rho1p, but has no effect on prenylation of endogenous Ras1p.
Murthi
Krishna K
KK
GPC Biotech, Inc., Department of Chemistry, 610 Lincoln Street, Waltham, MA 02451, USA. krishna.murthi@gpc-biotech.com
Smith
Susan E
SE
Kluge
Arthur F
AF
Bergnes
Gustave
G
Bureau
Patrick
P
Berlin
Vivian
V
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000201:enzymology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D008826:Microbial Sensitivity Tests; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017368:Protein Prenylation / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D009841:Oligonucleotides; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D020741:rho GTP-Binding Proteins; D000409:Alanine