title: [Synthesis and anti-Candida albicans properties of L-4-oxalysine-N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic-containing peptide analogues].
abstract: In order to improve the inhibitory activity of L-4-oxalysine(abbreviated as I-677) against clinically important pathogen Candida albicans, double-warheads peptide analogues containing I-677 and N3-4-methoxyfumaroyl-L-2,3-diaminopropanoic acid(FMDP) were designed based on the concept of "Illicit Transport" and peptide transport specificities of C. albicans. One compound of I-677-FMDP and seven compounds of I-677-AA-FMDP(AA = Nva, Leu, Val, Phe, Pro, D-Pgly, D, L-p-Cl-Phe) were synthesized and examined for antifungal activities. The results of anti-Candida albicans test in vitro of these double- warheads peptide analogues containing I-677 and FMDP showed very high activities against Candida albicans. The molar MIC (molar minimum inhibitory concentration) ratio of free I-677 to I-677-AA-FMDP is 40-770 and that of FMDP is 60-1130. The values of molar MIC of I-677-AA-FMDP varied from 6.56 x 10(-9) mol.disk-1 to 3.5 x 10(-10) mol.disk-1. The results of competitive antagonism studies indicated that I-677-AA-FMDP were transported into Candida albicans cells by the di-tripeptide permease and subsequently hydrolyzed by intracellular peptidases, releasing free I-677 and FMDP inside cells. The result of antienzymic degradation test in vitro of I-677-FMDP showed that compound I-677-FMDP was resistant to the hydrolysis by carboxypeptidase A.
authors.affiliation: Institute of Synthetic Medicine, Guangzhou Baiyunshan Pharmaceutical Co. Ltd., Guangzhou 510515.
authors.forename: S
authors.initials: S
authors.lastname: Feng
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005650:Fumarates / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D010455:Peptides; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005650:Fumarates; D010455:Peptides; D015091:beta-Alanine; C056276:N(3)-(4-methoxyfumaroyl)-2,3-diaminopropionic acid