N α-Fmoc-O, O-(dimethylphospho)-L-tyrosine fluoride: A convenient building block for the solid-phase synthesis of phosphotyrosyl peptides

Fretz, Heinz

doi:10.1007/bf02443530

Cited by 1 publication

(2 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The coupling of the amines (Chart ) onto the C-terminal Asn residue was accomplished after preactivation of the resin with TPTU/HOBt . Demethylation of the phosphate methyl groups was achieved with a 10-fold molar excess of TMSI in MeCN for 4 h at room temperature 17b. After this time, we could demonstrate that the demethylation was complete with all the peptides investigated.…”

Section: Chemistrymentioning

confidence: 97%

“…In a first step, N α -Fmoc-Asp-OAll was coupled through its side chain to the resin. On the basis of our previous studies concerning the synthesis of phosphotyrosine-containing peptides, Fmoc-Tyr(PO 3 Me 2 )-OH was incorporated using the same method. A prolonged reaction time (6 h) was necessary for the complete coupling of Fmoc-Tyr(PO 3 Me 2 )-OH onto the Ac 6 c residue.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Structure-Based Design and Synthesis of High Affinity Tripeptide Ligands of the Grb2-SH2 Domain

et al. 1998

Self Cite

View full text Add to dashboard Cite

The X-ray structure of the Grb2-SH2 domain in complex with a specific phosphopeptide ligand has revealed the existence of an extended hydrophobic area adjacent to the primary binding site of the ligand on the SH2 domain. This has been exploited to design hydrophobic C-terminal groups that improve the binding affinity of the minimal sequence pTyr-Ile-Asn recognized by the Grb2-SH2 domain. The most significant increase in affinity (25-fold compared to that of the reference peptide having a nonsubstituted carboxamide C-terminus) was obtained with a 3-naphthalen-1-yl-propyl group which was predicted to have the largest contact area with the SH2 domain hydrophobic region. This modification combined with replacement of the minimal sequence isoleucine residue by 1-aminocyclohexane carboxylic acid to stabilize the β-turn conformation required for recognition by the Grb2-SH2 domain resulted in the high affinity (47 nM in an ELISA assay) and selective phosphopeptide Ac-pTyr-Ac6c-Asn-NH(3-naphthalen-1-yl-propyl).

show abstract

Section: Chemistrymentioning

confidence: 97%

Section: Chemistrymentioning

confidence: 99%