168135-78-2

Basic information

• Product Name: methyl N^α-Fmoc-4-O-tyrosinate
• Synonyms: methyl N^α-Fmoc-4-O-tyrosinate
• CAS NO: 168135-78-2
• Molecular Weight: 631.723
• Mol File: 168135-78-2.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: methyl N^α-Fmoc-4-O-tyrosinate(CAS DataBase Reference)
• NIST Chemistry Reference: methyl N^α-Fmoc-4-O-tyrosinate(168135-78-2)
• EPA Substance Registry System: methyl N^α-Fmoc-4-O-tyrosinate(168135-78-2)

Safety Data

• Hazardous Substances Data: 168135-78-2(Hazardous Substances Data)

Upstream product

• 35207-75-1 di-tert-butyl diazomalonate 
• 82911-79-3 N-(fluorenyl-9-methoxycarbonyl)-L-tyrosine methyl ester 
• 60-18-4 L-tyrosine 
• 3417-91-2 L-tyrosine methyl ester HCl 
• 15960-79-9 di-tert-butyl 2-bromomalonate 

Downstream Products

• 174537-86-1 2-{4-[(S)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-methoxycarbonyl-ethyl]-phenoxy}-2-fluoro-malonic acid di-tert-butyl ester 
• 168135-77-1 N^α-Fmoc-O'-(O'',O''-di-tert-butyl-2-malonyl)tyrosine 
• 174537-81-6 N^α-Fmoc-4-O-[O',O''-di-tert-butyl-2-(2-fluoromalonyl)]-L-tyrosine 

Relevant articles and documents

New syntheses of tetrazolylmethylphenylalanine and O-malonyltyrosine as pTyr mimetics for the design of STAT3 dimerization inhibitors

Investigation within the pTyr-binding pocket of the STAT3 SH2 domain led us to develop a novel synthesis of two pTyr mimetics, l-tetrazolylmethylphenylalanine (l-Tmp) and l-O-malonyltyrosine (l-OMT), that were next incorporated in a high affinity ligand of STAT3 SH2 domain. Biological evaluation of peptidomimetics on STAT3 dimerization identified l-OMT as the first non-phosphorus pTyr mimetic so far reported against STAT3 SH2 domain, harboring an activity similar to that of the Pmp-containing reference peptidomimetic.

L-O-(2-Malonyl)tyrosine: A New Phosphotyrosyl Mimetic for the Preparation of Src Homology 2 Domain Inhibitory Peptides

Inhibition of Src homology 2 (SH2) domain-binding interactions affords one potential means of modulating protein-tyrosine kinase-dependent signaling.Small phosphotyrosyl (pTyr)-containing peptides are able to bind to SH2 domains and compete with larger pTyr peptides or native pTyr-containing protein ligands.Such pTyr-containing peptides are limited in their utility as SH2 domain inhibitors in vivo due to their hydrolytic lability to protein-tyrosine phosphatases (PTPs) and the poor cellular penetration of the ionized phosphate moiety.An important aspect of SH2 domain inhibitor design is the creation of pTyr mimetics which are stable to PTPs and have reasonable bioavailability.To date, most PTP-resistant pTyr mimetics which bind to SH2 domains are phosphonates such as (phosphonomethyl)phenylalanine (Pmp, 2), phenylalanine )(FPmp, 3) or phenylalanine (F2Pmp, 4).Herein we report the incorporation of a new non-phosphorus-containing pTyr mimetic, L-O-(2-malonyl)tyrosine (L-OMT, 5), into SH2 domain inhibitory peptides using the protected analogue L-Nα-Fmoc-O'-(O'',O''-di-tert-butyl-2-malonyl)tyrosine (6) and solid-phase peptide synthesis techniques.Five OMT-containing peptides were prepared against the following SH2 domains: the PI-3 kinase C-terminal p85 SH2 domain (Ac-D-(L-OMT)-V-P-M-L-amide, 10, IC50 = 14.2 μM), the Src SH2 domain (Ac-Q-(L-OMT)-E-E-I-P-amide, 11, IC50 = 25 μM, and Ac-Q-(L-OMT)-(L-OMT)-E-I-P-amide, 14, IC50 = 23 μM), the Grb2 SH2 domain (Ac-N-(L-OMT)-V-N-I-E-amide, 12, IC50 = 120 μM), and the N-terminal SH-PTP2 SH2 domain (Ac-L-N-(L-OMT)-I-D-L-D-L-V-amide, 13, IC50 = 22.0 μM.These results show that peptides 10, 11, 13, and 14 have reasonable affinity for their respective SH2 domains, with the IC50 value for the SH-PTP2 SH2 domain-directed peptide 13 being equivalent to that previously observed for the corresponding F2Pmp-containing peptide.OMT may afford a new structural starting point for the development of novel and useful SH2 domain inhibitors.