Synthesis of potent water-soluble tissue transglutaminase inhibitors.
Dipeptide-based sulfonium peptidylmethylketones derived from 6-diazo-5-oxo-L-norleucine (DON) have been investigated as potential water-soluble inhibitors of extracellular transglutaminase. The lead compounds were prepared in four steps and exhibited potent activity against tissue transglutaminase.
Griffin
Martin
M
School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. m.griffin@aston.ac.uk
Mongeot
Alexandre
A
Collighan
Russell
R
Saint
Robert E
RE
Jones
Richard A
RA
Coutts
Ian G C
IG
Rathbone
Daniel L
DL
D020134:Catalytic Domain; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003980:Diazooxonorleucine / Q000737:chemistry*; D015195:Drug Design; D000431:Ethanol / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D020128:Inhibitory Concentration 50; D007659:Ketones / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods; D010455:Peptides / Q000737:chemistry; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012995:Solubility; D013053:Spectrophotometry / Q000379:methods; D011503:Transglutaminases / Q000037:antagonists & inhibitors*; D014867:Water / Q000737:chemistry*
D007659:Ketones; D010455:Peptides; D003980:Diazooxonorleucine; D014867:Water; D000431:Ethanol; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins