N-methylated sst 2 selective somatostatin cyclic peptide analogue as a potent candidate for treating neurogenic inflammation

Jayanta Chatterjee; Burkhardt Laufer; Johannes G. Beck; Zsuzsanna Helyes; Erika Pintér; János Szolcsányi; Aniko Horvath; Jozsef Mandl; Jean C. Reubi; György Kéri; Horst Kessler

doi:10.1021/ml200032v

N-methylated sst ₂ selective somatostatin cyclic peptide analogue as a potent candidate for treating neurogenic inflammation

Jayanta Chatterjee, Burkhardt Laufer, Johannes G. Beck, Zsuzsanna Helyes, Erika Pintér, János Szolcsányi, Aniko Horvath, Jozsef Mandl, Jean C. Reubi, György Kéri, Horst Kessler

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Abstract

A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst ₂). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.

Original language	English
Pages (from-to)	509-514
Number of pages	6
Journal	ACS Medicinal Chemistry Letters
Volume	2
Issue number	7
DOIs	https://doi.org/10.1021/ml200032v
State	Published - 14 Jul 2011

Keywords

N-methylated peptide
Somatostatin
cyclic peptide
multiple N-methylation
neurogenic inflammation
sst

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title = "N-methylated sst 2 selective somatostatin cyclic peptide analogue as a potent candidate for treating neurogenic inflammation",

abstract = "A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst 2). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.",

keywords = "N-methylated peptide, Somatostatin, cyclic peptide, multiple N-methylation, neurogenic inflammation, sst",

author = "Jayanta Chatterjee and Burkhardt Laufer and Beck, {Johannes G.} and Zsuzsanna Helyes and Erika Pint{\'e}r and J{\'a}nos Szolcs{\'a}nyi and Aniko Horvath and Jozsef Mandl and Reubi, {Jean C.} and Gy{\"o}rgy K{\'e}ri and Horst Kessler",

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doi = "10.1021/ml200032v",

language = "English",

volume = "2",

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journal = "ACS Medicinal Chemistry Letters",

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T1 - N-methylated sst 2 selective somatostatin cyclic peptide analogue as a potent candidate for treating neurogenic inflammation

AU - Chatterjee, Jayanta

AU - Laufer, Burkhardt

AU - Beck, Johannes G.

AU - Helyes, Zsuzsanna

AU - Pintér, Erika

AU - Szolcsányi, János

AU - Horvath, Aniko

AU - Mandl, Jozsef

AU - Reubi, Jean C.

AU - Kéri, György

AU - Kessler, Horst

PY - 2011/7/14

Y1 - 2011/7/14

N2 - A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst 2). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.

AB - A focused multiply N-methylated library of a cyclic hexapeptidic somatostatin analogue: MK678 cyclo(-MeAYwKVF-) was generated, which resulted in the unexpected observation of an efficacious tetra-N-methylated analogue, cyclo(-MeAYMewMeKVMeF-) with a potent inhibitory action on sensory neuropeptide release in vitro and on acute neurogenic inflammatory response in vivo. The analogue shows selectivity toward somatostatin receptor subtype 2 (sst 2). Extensive 2D NMR spectroscopy and molecular dynamics simulation revealed the solution conformation of the analogue, which can be adopted as a lead for the further structure-activity relationship studies targeting neurogenic inflammation.

KW - N-methylated peptide

KW - Somatostatin

KW - cyclic peptide

KW - multiple N-methylation

KW - neurogenic inflammation

KW - sst

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DO - 10.1021/ml200032v

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ER -

N-methylated sst ₂ selective somatostatin cyclic peptide analogue as a potent candidate for treating neurogenic inflammation

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Keywords

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