title: Exploring structure-activity relationships around the phosphomannose isomerase inhibitor AF14049 via combinatorial synthesis.
abstract: Phosphomannose Isomerase (PMI) has been shown by genetic methods to be an essential enzyme in fungal cell wall biosynthesis. The PMI inhibitor AF14049 was discovered as an unanticipated side product from high-throughput library screening against the enzyme from C, albicans. Solid-phase synthetic methods were developed and a series of libraries and discrete analogs synthesized to explore SAR around AF14049.
authors.affiliation: Affymax Research Institute, Palo Alto, CA 94304, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bhandari
authors.forename: D G
authors.initials: DG
authors.lastname: Jones
authors.forename: J R
authors.initials: JR
authors.lastname: Schullek
authors.forename: K
authors.initials: K
authors.lastname: Vo
authors.forename: C A
authors.initials: CA
authors.lastname: Schunk
authors.forename: L L
authors.initials: LL
authors.lastname: Tamanaha
authors.forename: D
authors.initials: D
authors.lastname: Chen
authors.forename: Z
authors.initials: Z
authors.lastname: Yuan
authors.forename: M C
authors.initials: MC
authors.lastname: Needels
authors.forename: M A
authors.initials: MA
authors.lastname: Gallop
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002176:Candida albicans / Q000201:enzymology; D002473:Cell Wall / Q000378:metabolism; D019992:Databases as Topic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007189:Indans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D008359:Mannose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: C116722:AF 14049; D000577:Amides; D004791:Enzyme Inhibitors; D007189:Indans; D007202:Indicators and Reagents; D008359:Mannose-6-Phosphate Isomerase