Demonstration of a 1-3 disulfide bond in a synthetic nonapeptide derived from the signal sequence and N-terminus of human gamma-interferon.
The nonapeptide Cys-Tyr-Cys-Gln-Asp-Pro-Tyr-Val-Lys was prepared by solid-phase peptide synthesis under oxidizing conditions. Fast atom bombardment mass spectrometric analysis of the untreated molecule produced an ion consistent with a structure involving an intramolecular disulfide bond between Cys(1) and Cys(3). Mass spectra of the peptide after treatment with 2-mercaptoethanol gave signals corresponding to the reduced disulfide form of the peptide and to a mixed disulfide of the peptide with 2-mercaptoethanol. Molecular mechanics calculations of the conformation of the 11-membered ring formed by disulfide bond closure predicted a discrete, low-energy structure resembling the locus of a gamma turn. We hypothesize that this structure may be important in the recognition and cleavage of the signal sequence of the parent molecule.
Pramanik
B
B
Schering Corporation, Bloomfield, New Jersey 07003.
Tsarbopoulos
A
A
Labdon
J E
JE
Czarniecki
M
M
Nagabhushan
T L
TL
Trotta
P P
PP
D002851:Chromatography, High Pressure Liquid; D004220:Disulfides; D007371:Interferon-gamma / Q000648:ultrastructure*; D013058:Mass Spectrometry; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis; D011487:Protein Conformation; D021382:Protein Sorting Signals; D013816:Thermodynamics
D004220:Disulfides; D009842:Oligopeptides; D021382:Protein Sorting Signals; D007371:Interferon-gamma