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Structure determination and by‐product profile of the NK 2 receptor antagonist nepadutant, a bicyclic glycopeptide
Author(s) -
Weißhoff Hardy,
Nagel Thomas,
Hänsicke Andre,
Zschunke Adolf,
Mügge Clemens
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02203-7
Subject(s) - bicyclic molecule , chemistry , dipeptide , isomerization , stereochemistry , moiety , nuclear magnetic resonance spectroscopy , peptide , molecule , residue (chemistry) , organic chemistry , biochemistry , catalysis
We have synthesized and fully characterized the NK 2 receptor antagonist nepadutant and its by‐products using nuclear magnetic resonance (NMR) and restrained molecular dynamics. The agent consists of an active bicyclic hexapeptide combined with a sugar residue. Analysis of the high‐performance liquid chromatogram and the mass spectroscopy spectra yields traces of three by‐products with the same molecular weight as the main product. The conformation of the molecules in the bicyclic hexapeptide segment, the active region, is well defined, whereas the sugar moiety is disordered. For the peptide region of nepadutant and all of its by‐products, the NMR observables can be described by a single backbone conformation, more specifically a βI, βII‐turn arrangement. The active dipeptide unit Trp–Phe occupies the i +1 and i +2 position of a βI‐turn. The by‐product profile is characterized by different forms of sugars which are caused mainly by isomerization in the process of ring opening.