60079-69-8Relevant academic research and scientific papers
The use of peptiCLEC-TR in the preparation of dipeptides
Faulconbridge, Susan J.,Holt, Karen E.,Lock, Christopher J.,Taylor, Stephen J. C.,Woods, Martin
, p. 563 - 566 (2000)
Dipeptides are important intermediates in many pharmaceutical products. To support a research programme on matrix metalloproteinases (MMP) we needed to prepare the dipeptide, Leu-Phe-NHMe (3). Chemical methods provided the material but not to the quality
Peptidyl 3-substituted 1-hydroxyureas as isosteric analogues of succinylhydroxamate MMP inhibitors
Campestre, Cristina,Tortorella, Paolo,Agamennone, Mariangela,Preziuso, Serena,Biasone, Alessandro,Nuti, Elisa,Rossello, Armando,Gallina, Carlo
, p. 1008 - 1014 (2008/09/20)
To evaluate N-hydroxyurea as zinc binding group in the design of MMP inhibitors, two peptidyl 1-hydroxyureas were prepared by N-hydroxycarbamoylation of the diastereomeric dipeptides H-Leu-Phe-NHMe and H-d-Leu-Phe-NHMe. Peptidyl 1-hydroxyureas were more potent than the parent peptides, but dramatically weaker (4-5 orders of magnitude) than the isosteric (R)-succinylhydroxamate analogue, which displays IC50 in the range of nM vs MMP-1, -3, -7 and sub-nM vs MMP-2, -8, and -9. The peptidyl 1-hydroxyurea 1a attained an IC50 of 20 μM vs MMP-9, and substantially approaches inhibition of known N-hydroxyureas based on aminoacids or peptides against other zinc metalloenzymes and non-peptidic N-hydroxyureas against MMPs. Strong preference of the O-N1-C{double bond, long}O unit for the antiperiplanar amide bond conformation seems to be the major limit for more effective zinc chelation. Methylation of a peptidyl 1-hydroxyurea at N3, to promote the synperiplanar O-N1-C{double bond, long}O conformation required for zinc chelation and improve affinity, resulted in release of a methylimidazolidine-2,4-dione through an undesired intramolecular reaction reminiscent of the Edman peptide degradation.
A novel series of matrix metalloproteinase inhibitors for the treatment of inflammatory disorders
Baxter, Andrew D.,Bird, John,Bhogal, Ranjev,Massil, Tracy,Minton, Kevin J.,Montana, John,Owen, David A.
, p. 897 - 902 (2007/10/03)
The preparation of a novel series of matrix metalloproteinase inhibitors is described, based on the use of a mercaptoacyl zinc binding moiety. The compounds have been tested in a model of rheumatoid arthritis and show good oral activity.
