Structure-activity relationship of a novel peptide substrate for p60c-src protein tyrosine kinase |
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Authors: | Qiang Lou Jinzi Wu Sydney E Salmon and Kit S Lam |
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Institution: | (1) Arizona Cancer Center, University of Arizona, 1515 N. Campbell Avenue, 85724 Tucson, AZ, U.S.A.;(2) Department of Medicine, University of Arizona, 1515 N. Campbell Avenue, 85724 Tucson, AZ, U.S.A.;(3) Department of Microbiology, University of Arizona College of Medicine, 85724 Tucson, AZ, U.S.A.;(4) Department of Immunology, University of Arizona College of Medicine, 85724 Tucson, AZ, U.S.A.;(5) Selectide Corporation, a Subsidiary of Hoechst Marion Russell, 1580 East Hanley Boulevard, 85737 Tucson, AZ, U.S.A. |
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Abstract: | Summary We recently reported the identification of a peptide (YIYGSFK) as an efficient substrate for p60c-src using a random combinatorial peptide library screening method. Over 70 analogues of YIYGSFK were designed and synthesized on beads and their phosphorylation on solid phase by p60c-src was quantitated by the PhosphorImager. A hydrophobic l-amino acid in position 2 and a basic amino acid in position 7 proved crucial for activity as a substrate. In addition, the l-tyrosine residue at position 3 was critical as the phosphorylation site and was found to be stereospecific, as substitution with the d-enantiomer at this position rendered the peptide totally inactive.Abbreviations
-alanine
-
-aminocaproic acid
- Ac
N-acetyl
- BOP
benzotriazol-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate
- BSA
bovine serum albumin
- Cha
l-cyclohexylalanine
- Chg
l-cyclohexylglycine
- Dab
l-diaminobutyric acid
- Dap
l-diaminoproprionic acid
- DIEA
N,N-diisopropylethylamine
- DMF
dimethylformamide
- Fmoc
fluorenylmethyloxycarbonyl
- HOBt
N-hydroxybenzotriazole
- MeF
N-methyl-l-phenylalanine
- MeG
N-methylglycine
- MeI
N-methyl-l-isoleucine
- MES
2-N-morpholinolethanesulfonic acid
- Nle
l-norleucine
- Orn
l-ornithine
- TFA
trifluoroacetic acid
- Z-Sar
benzyloxycarbonyl-sarcosine
- Z-Tyr
benzyloxycarbonyl-l-tyrosine |
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Keywords: | Combinatorial libraries Peptide substrate p60c-src Protein tyrosine kinases |
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