TY - JOUR
T1 - A novel 3-step enantioselective synthesis of pyrenylalanine with subsequent incorporation into opioid, CCK, and melanotropin ligands
AU - Alves, Isabel
AU - Cowell, Scott
AU - Lee, Yeon Sun
AU - Tang, Xuejun
AU - Davis, Peg
AU - Porreca, Frank
AU - Hruby, Victor J
N1 - Funding Information:
This research was supported in part by grants from the US-Public Health Service DK17420 and DA06284. We also acknowledge Dr. Xuyuan Gu and Dr. Malcom Kavarana for helpful discussions on the NMR work, and Minying Cai for help with the melanocortin binding assays. The opinions expressed are those of the authors and do not necessary reflect those of the USPHS.
PY - 2004/5/28
Y1 - 2004/5/28
N2 - Pyrene possesses unique spectroscopic properties such as a high quantum yield, a long half-life in the excited state, and the ability to form excimers when in proximity to each other in the excited state. These properties allow pyrenylalanine, which is a pyrene moiety incorporated into an amino acid, to be used as a fluorescent probe in peptides and proteins [J. Chem. Soc. Perkin Trans. 2 (1995) 1133; J. Am. Chem. Soc. 111 (1989) 6790; J. Chem. Soc. Perkin Trans. 2 (1997) 517]. The common route for the synthesis of pyrenylalanine involves 5 steps [Macromolecules 18 (1985) 882], with subsequent separation of the two isomers by recrystallization. This paper reports a novel 3-step asymmetric synthesis of pyrenylalanine with high enantioselectivity, good yields, and facile isomer purification. After synthesis, pyrenylalanine was incorporated into a series of opioid, CCK, and melanotropin peptide ligands in order to study the effects of aromaticity, lipophilicity, and steric properties on their potency and efficacy at their corresponding biological receptors. The change in binding and efficacy of the labeled ligands as compared to the unlabeled ligands demonstrates the possible role of lipophilicity/aromaticity in the binding and signal transduction of the ligand-receptor interaction.
AB - Pyrene possesses unique spectroscopic properties such as a high quantum yield, a long half-life in the excited state, and the ability to form excimers when in proximity to each other in the excited state. These properties allow pyrenylalanine, which is a pyrene moiety incorporated into an amino acid, to be used as a fluorescent probe in peptides and proteins [J. Chem. Soc. Perkin Trans. 2 (1995) 1133; J. Am. Chem. Soc. 111 (1989) 6790; J. Chem. Soc. Perkin Trans. 2 (1997) 517]. The common route for the synthesis of pyrenylalanine involves 5 steps [Macromolecules 18 (1985) 882], with subsequent separation of the two isomers by recrystallization. This paper reports a novel 3-step asymmetric synthesis of pyrenylalanine with high enantioselectivity, good yields, and facile isomer purification. After synthesis, pyrenylalanine was incorporated into a series of opioid, CCK, and melanotropin peptide ligands in order to study the effects of aromaticity, lipophilicity, and steric properties on their potency and efficacy at their corresponding biological receptors. The change in binding and efficacy of the labeled ligands as compared to the unlabeled ligands demonstrates the possible role of lipophilicity/aromaticity in the binding and signal transduction of the ligand-receptor interaction.
KW - Cholecystokinin
KW - Enantioselective amino acid synthesis
KW - Melanocortin
KW - Opioid
KW - Pyrenylalanine
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U2 - 10.1016/j.bbrc.2004.04.033
DO - 10.1016/j.bbrc.2004.04.033
M3 - Article
C2 - 15120606
AN - SCOPUS:2142827076
SN - 0006-291X
VL - 318
SP - 335
EP - 340
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -