Solid phase synthesis of a biased mini tetrapeptoid-library for the discovery of monodentate ITAM mimics as ZAP-70 inhibitors.
The biased library was composed of a novel phosphotyrosine mimic fixed in the P1 position of a tetrapeptoid and combined with three lipophilic N-substituents at the remaining positions giving a total of 27 single compounds. Screening for ZAP-70 antagonism identified 8 as a novel selective monodentate ZAP-70 antagonist and lead in the search for new immunosuppressive drugs.
Révész
L
L
Preclinical Research Novartis, Basel, Switzerland. laszlo.revesz@pharma.novartis.com
Bonne
F
F
Manning
U
U
Zuber
J F
JF
D006801:Humans; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D019151:Peptide Library; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011971:Receptors, Immunologic / Q000737:chemistry*; D014443:Tyrosine / Q000737:chemistry; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains
D009842:Oligopeptides; D019151:Peptide Library; D011971:Receptors, Immunologic; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human