Synthesis of (2R,3S) 3-amino-4-mercapto-2-butanol, a threonine analogue for covalent inhibition of sortases.
L-Threonine 2 was converted in seven steps into the protected aminomercaptoalcohol 8, a threonine mimic. This compound 8 was coupled to various oligopeptides to produce two different tetrapeptide analogues, for example, 11 and 17, which were shown to inhibit the Sortase enzymes (SrtA and SrtB) via covalent attachment of the thiol groups of 11 and 17 to the catalytically active cysteine residue of the Sortase enzymes.
Jung
Michael E
ME
Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Ave, Los Angeles, CA 90095, USA. jung@chem.ucla.edu
Clemens
Jeremy J
JJ
Suree
Nuttee
N
Liew
Chu Kong
CK
Pilpa
Rosemarie
R
Campbell
Dean O
DO
Clubb
Robert T
RT
D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000440:Butanols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013912:Threonine / Q000031:analogs & derivatives* / Q000737:chemistry
C506372:(2R,3S) 3-amino-4-mercapto-2-butanol; D001426:Bacterial Proteins; D000440:Butanols; D004791:Enzyme Inhibitors; D013912:Threonine; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases