Abstract
Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus- containing phosphotyrosyl (pTyr) mimetics, which utilize carboxylic groups to provide functionality normally afforded by the pTyr phosphate group. To demonstrate the utility of these analogues, the protein-tyrosine phosphatase- directed peptides Ac-D-A-D-E-X-L-amide (28 - 30) were prepared, where X = pTyr mimetic. In the case where X = 3-carboxy-4-(O-carboxymethyl)-L-tyrosine (8) a K(i) value of 3.6 μM was obtained against PTP1, which equals the Km of the parent pTyr containing peptide. Besides tyrosine phosphatases, these analogues may be useful in a number of contexts, including SH2 domain and phosphotyrosine binding domain systems.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9981-9994 |
| Number of pages | 14 |
| Journal | Tetrahedron |
| Volume | 54 |
| Issue number | 34 |
| DOIs | |
| State | Published - Aug 20 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
- Organic Chemistry
- Drug Discovery
Cite this
Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides. / Burke, Terrence R.; Yao, Zhu Jun; Zhao, He; Milne, George W A; Wu, Li; Zhang, Zhong-Yin; Voigt, Johannes H.
In: Tetrahedron, Vol. 54, No. 34, 20.08.1998, p. 9981-9994.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enantioselective synthesis of nonphosphorus-containing phosphotyrosyl mimetics and their use in the preparation of tyrosine phosphatase inhibitory peptides
AU - Burke, Terrence R.
AU - Yao, Zhu Jun
AU - Zhao, He
AU - Milne, George W A
AU - Wu, Li
AU - Zhang, Zhong-Yin
AU - Voigt, Johannes H.
PY - 1998/8/20
Y1 - 1998/8/20
N2 - Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus- containing phosphotyrosyl (pTyr) mimetics, which utilize carboxylic groups to provide functionality normally afforded by the pTyr phosphate group. To demonstrate the utility of these analogues, the protein-tyrosine phosphatase- directed peptides Ac-D-A-D-E-X-L-amide (28 - 30) were prepared, where X = pTyr mimetic. In the case where X = 3-carboxy-4-(O-carboxymethyl)-L-tyrosine (8) a K(i) value of 3.6 μM was obtained against PTP1, which equals the Km of the parent pTyr containing peptide. Besides tyrosine phosphatases, these analogues may be useful in a number of contexts, including SH2 domain and phosphotyrosine binding domain systems.
AB - Three new L-amino acid analogues 12, 18 and 25 have been prepared in protected form suitable for incorporation into peptides by solid-phase synthesis using Fmoc protocols. These agents represent nonphosphorus- containing phosphotyrosyl (pTyr) mimetics, which utilize carboxylic groups to provide functionality normally afforded by the pTyr phosphate group. To demonstrate the utility of these analogues, the protein-tyrosine phosphatase- directed peptides Ac-D-A-D-E-X-L-amide (28 - 30) were prepared, where X = pTyr mimetic. In the case where X = 3-carboxy-4-(O-carboxymethyl)-L-tyrosine (8) a K(i) value of 3.6 μM was obtained against PTP1, which equals the Km of the parent pTyr containing peptide. Besides tyrosine phosphatases, these analogues may be useful in a number of contexts, including SH2 domain and phosphotyrosine binding domain systems.
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UR - http://www.scopus.com/inward/citedby.url?scp=0032552183&partnerID=8YFLogxK
U2 - 10.1016/S0040-4020(98)00590-0
DO - 10.1016/S0040-4020(98)00590-0
M3 - Article
VL - 54
SP - 9981
EP - 9994
JO - Tetrahedron
JF - Tetrahedron
SN - 0040-4020
IS - 34
ER -