186689-03-2Relevant academic research and scientific papers
Synthesis of new DOPA derivative from l-tyrosine for construction of bioactive compound
Sun, Dequn,Wan, Peihong,Zhang, Guoqing,Luo, Min
, p. 9407 - 9408 (2013/11/19)
A practical synthetic method of new DOPA derivative was developed with L-tyrosine as starting material. The new DOPA analogue could be used in building bioactive compounds.
Peptide-based activity-based probes (ABPs) for target-specific profiling of protein tyrosine phosphatases (PTPs)
Kalesh, Karunakaran A.,Tan, Lay Pheng,Lu, Kai,Gao, Liqian,Wang, Jigang,Yao, Shao Q.
supporting information; experimental part, p. 589 - 591 (2010/05/01)
Synthesis of a novel unnatural amino acid (2-FMPT) for the solid-phase synthesis of peptide-based probes suitable for target-specific activity-based profiling of protein tyrosine phosphatases from crude proteomes is reported.
Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3′-substituted tyrosine derivatives
Song, Yan-Li,Peach, Megan L.,Roller, Peter P.,Qiu, Su,Wang, Shaomeng,Long, Ya-Qiu
, p. 1585 - 1596 (2007/10/03)
The growth factor receptor-bound protein 2 (Grb2) is an SH2 domain-containing docking module that represents an attractive target for anticancer therapeutic intervention. An impressive number of synthetic Grb2-SH2 domain inhibitors have been identified; however, clinical agents operating by this mechanism are lacking, due in part to the unique requirement of anionic phosphate-mimicking functionality for high SH2 domain-binding affinity or the extended peptide nature of most inhibitors. In the current study, a new binding motif was successfully developed by the incorporation of 3′-substituted tyrosine derivatives into a simplified nonphosphorylated cyclic pentapeptide scaffold (4), which resulted in high affinity Grb2-SH2 inhibitors without any phosphotyrosine or phosphotyrosine mimetics. The new L-amino acid analogues bearing an additional nitro, amino, hydroxy, methoxy or carboxy group at the 3′-position of the phenol ring of tyrosine were prepared in an orthogonally protected form suitable for solid-phase peptide synthesis using Fmoc protocols. The incorporation of these residues into cyclic peptides composed of a five-amino acid sequence motif, Xx′-Leu-(3′- substituted-Tyr)-Ac6c-Asn, provided a brand new class of nonphosphorylated Grb2 SH2 domain inhibitors with reduced size, charge and peptidic character. The highest binding affinity was exhibited by the 3′-aminotyrosine (3′-NH2-Tyr)-containing (R)-sulfoxide-cyclized pentapeptide (10b) with an IC50 = 58 nM, the first example with low-nanomolar affinity for a five-amino acid long sequence binding to Grb2-SH2 domain free of any phosphotyrosine or phosphotyrosine mimics. However, the incorporation of 3′-NO2-Tyr, 3′-OH-Tyr or 3′-OCH3-Tyr surrogates in the pentapeptide scaffold is detrimental to Grb2-SH2 binding. These observations were rationalized using molecular modeling. More significantly, the best Grb2-SH2 inhibitor 10b showed excellent activity in inhibiting the growth of erbB2-dependent MDA-MB-453 tumor cell lines with an IC50 value of 19 nM. This study is the first attempt to identify novel nonphosphorylated high affinity Grb2 SH2 inhibitors by the utilization of 3′-substituted tyrosine derivatives, providing a promising new strategy and template for the development of non-pTyr-containing Grb2-SH2 domain antagonists with potent cellular activity, which potentially may find value in chemical therapeutics for erbB2-related cancers.
Utilization of 3′-carboxy-containing tyrosine derivatives as a new class of phosphotyrosyl mimetics in the preparation of novel non-phosphorylated cyclic peptide inhibitors of the Grb2-SH2 domain
Song, Yan-Li,Tan, Jinzhi,Luo, Xiao-Min,Long, Ya-Qiu
, p. 659 - 666 (2007/10/03)
A new class of phosphotyrosyl (pTyr) mimetics, distinct from the conventional pTyr mimetic design of adding non-hydrolyzable acidic functionalities to the 4′-position of phenylalanine, was created by introducing carboxy-containing groups to the 3′-positio
Synthesis of tyrosine derivatives for saframycin MX1 biosynthetic studies
Schmidt, Eric W.,Nelson, James T.,Fillmore, John P.
, p. 3921 - 3924 (2007/10/03)
Saframycin MX1 and structural relatives are natural anticancer agents isolated from bacteria and marine invertebrates. For biosynthetic studies and to make a library of modified natural products, a series of tyrosine derivatives were synthesized in a conc
