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ACS Infect Dis

Title:		N-Methylation of Amino Acids in Gelatinase Biosynthesis-Activating Pheromone Identifies Key Site for Stability Enhancement with Retention of the Enterococcus faecalis fsr Quorum Sensing Circuit Response
Author(s):		McBrayer DN; Gantman BK; Tal-Gan Y;
Address:		"Department of Chemistry , University of Nevada, Reno , 1664 N. Virginia Street , Reno , Nevada 89557 , United States"
Journal Title:		ACS Infect Dis
Year:		2019
Volume:		20190419
Issue:		6
Page Number:		1035 - 1041
DOI:		10.1021/acsinfecdis.9b00097
ISSN/ISBN:		2373-8227 (Electronic) 2373-8227 (Linking)
Abstract:		"The growing prevalence of multiantibiotic-resistant bacteria necessitates looking at potential alternative approaches for attenuating infections by bacteria while reducing the rate of antibiotic resistance development. Enterococcus faecalis is responsible for a large percentage of clinical enterococci infections, and its pathogenicity has been demonstrated to be influenced by quorum sensing (QS). In this study, we report the systematic study of the relationship between backbone hydrogens and the ability to activate the FsrC receptor. We demonstrate that N-methylation was particularly well-tolerated at one site (Phe7) and granted stability against protease digestion, increasing the peptide half-life relative to the native signal by more than 6-fold. The inclusion of the N-Me-Phe7 modification may be useful for improving the pharmacological properties of E. faecalis QS inhibitors as part of the development of future therapeutic candidates"
Keywords:		"Amino Acids/chemistry Bacterial Proteins/*metabolism Enterococcus faecalis/genetics/*metabolism Lactones/*metabolism Methylation Peptides, Cyclic/*metabolism Quorum Sensing/*drug effects gelatinase biosynthesis-activating pheromone metabolic stability pep;"
Notes:		"MedlineMcBrayer, Dominic N Gantman, Brooke K Tal-Gan, Yftah eng P20 GM103440/GM/NIGMS NIH HHS/ R35 GM128651/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2019/04/12 ACS Infect Dis. 2019 Jun 14; 5(6):1035-1041. doi: 10.1021/acsinfecdis.9b00097. Epub 2019 Apr 19"