New PDMP analogues inhibit process outgrowth in an insect cell line

Jacob P. Slavish; Donna K. Friel; Lynne A. Oland; Robin Polt

doi:10.1016/j.bmcl.2004.01.013

New PDMP analogues inhibit process outgrowth in an insect cell line

Jacob P. Slavish, Donna K. Friel, Lynne A. Oland, Robin Polt

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

D-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (D-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New D-threo-PDMP analogues were synthesized from D-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than D-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies.

Original language	English (US)
Pages (from-to)	1487-1490
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	6
DOIs	https://doi.org/10.1016/j.bmcl.2004.01.013
State	Published - Mar 22 2004

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2004.01.013

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@article{e05afab57a3b4b779d6a9dcd3e2b89f3,

title = "New PDMP analogues inhibit process outgrowth in an insect cell line",

abstract = "D-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (D-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New D-threo-PDMP analogues were synthesized from D-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than D-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies.",

author = "Slavish, {Jacob P.} and Friel, {Donna K.} and Oland, {Lynne A.} and Robin Polt",

note = "Funding Information: We thank the U.S. Army (DAMD 17-99-1-9539) for financial support. Support for L.A.O. was partially supplied by NIH (P01-NS28495). D.K.F. was partially supported by a McNair Fellowship.",

year = "2004",

month = mar,

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doi = "10.1016/j.bmcl.2004.01.013",

language = "English (US)",

volume = "14",

pages = "1487--1490",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

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T1 - New PDMP analogues inhibit process outgrowth in an insect cell line

AU - Slavish, Jacob P.

AU - Friel, Donna K.

AU - Oland, Lynne A.

AU - Polt, Robin

N1 - Funding Information: We thank the U.S. Army (DAMD 17-99-1-9539) for financial support. Support for L.A.O. was partially supplied by NIH (P01-NS28495). D.K.F. was partially supported by a McNair Fellowship.

PY - 2004/3/22

Y1 - 2004/3/22

N2 - D-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (D-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New D-threo-PDMP analogues were synthesized from D-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than D-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies.

AB - D-threo-1-Phenyl-2-aminodecanoyl-3-morpholinopropanol (D-threo-PDMP) has previously been shown to inhibit the biosynthesis of glycosphingolipids (GSLs) in mammals and mammalian cell lines by the inhibition of glucosylceramide synthase. New D-threo-PDMP analogues were synthesized from D-serine, and found to suppress neurite extension in an embryonic insect cell line from the moth Manduca sexta, and in explanted neural tissue from insect pupae. Inhibition occurred at lower concentrations than D-threo-PDMP. The observed suppression of neurite formation was found to be reversible after the removal of the compounds. Due to their small size and short life cycle, M. sexta is shown to be an ideal model organism for studies of GSL effects in cellular development, and for drug development studies.

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U2 - 10.1016/j.bmcl.2004.01.013

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AN - SCOPUS:1542345052

SN - 0960-894X

VL - 14

SP - 1487

EP - 1490

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 6

ER -

New PDMP analogues inhibit process outgrowth in an insect cell line

Abstract

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