Abstract
We have recently determined that -Ile-Tyr-were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase (Lou, Q. et al., Lett. Peptide Sci., 1995, 2, 289). Here, we report on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine). This secondary library was screened for its ability to be phosphorylated by p60c-src PTK using [γ32P]ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 677-682 |
| Number of pages | 6 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 4 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1996 |
| Externally published | Yes |
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Keywords
- Combinatorial libraries
- p60
- Peptide substrate
- Protein tyrosine kinase
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Organic Chemistry
- Drug Discovery
- Pharmaceutical Science
Cite this
Dentification of GIYWHHY as a novel peptide substrate for human p60c-src protein tyrosine kinase. / Lou, Qiang; Leftwich, Margaret E.; Lam, Kit.
In: Bioorganic and Medicinal Chemistry, Vol. 4, No. 5, 05.1996, p. 677-682.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dentification of GIYWHHY as a novel peptide substrate for human p60c-src protein tyrosine kinase
AU - Lou, Qiang
AU - Leftwich, Margaret E.
AU - Lam, Kit
PY - 1996/5
Y1 - 1996/5
N2 - We have recently determined that -Ile-Tyr-were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase (Lou, Q. et al., Lett. Peptide Sci., 1995, 2, 289). Here, we report on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine). This secondary library was screened for its ability to be phosphorylated by p60c-src PTK using [γ32P]ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate.
AB - We have recently determined that -Ile-Tyr-were the two critical residues as a peptide substrate for p60c-src protein tyrosine kinase (Lou, Q. et al., Lett. Peptide Sci., 1995, 2, 289). Here, we report on the design and synthesis of a secondary 'one-bead, one-compound' combinatorial peptide library based on this dipeptide motif (XIYXXXX, where X = all 19 eukaryotic amino acids except for cysteine). This secondary library was screened for its ability to be phosphorylated by p60c-src PTK using [γ32P]ATP as a tracer. Five of the strongest [32P]-labeled peptide-beads were identified and microsequenced: GIYWHHY, KIYDDYE, EIYEENG, EIYEEYE, and YIYEEED. A solid-phase phosphorylation assay was used to evaluate the structure-activity relationship of GIYWHHY. It was determined that Ile2, Tyr3, His5, and His6 were crucial for its activity as a substrate.
KW - Combinatorial libraries
KW - p60
KW - Peptide substrate
KW - Protein tyrosine kinase
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UR - http://www.scopus.com/inward/citedby.url?scp=0029896432&partnerID=8YFLogxK
U2 - 10.1016/0968-0896(96)00063-6
DO - 10.1016/0968-0896(96)00063-6
M3 - Article
C2 - 8804533
AN - SCOPUS:0029896432
VL - 4
SP - 677
EP - 682
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
SN - 0968-0896
IS - 5
ER -