International Journal of Biochemistry and Biophysics Vol. 9(1), pp. 8 - 15
DOI: 10.13189/ijbb.2021.090102
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Signature of Glycylglutamic Acid Structure


Amanda Hoff 1,2, Nigam Rath 3, John Lisko 1, Matthias Zeller 1,4, Ganesaratnam K. Balendiran 1,*
1 Department of Chemistry, Youngstown State University, Youngstown, OH 44555, USA
2 Northwestern Medicine Central DuPage Hospital, Winfield, IL 60190, USA
3 Department of Chemistry and Biochemistry and Center for Nanoscience, University of Missouri, St. Louis, MO 63121, USA
4 Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA

ABSTRACT

Background: Glutamate (Glu) is of great interest in biomedical research. It is considered a biomarker in diabetes, which may potentially contribute to the development of autism in genetically vulnerable human populations, and it is found in relation to advanced glycation end products (AGEs) [1]. Additionally, Glu plays an active role in the function of ligand-gated ion channel glutamate receptors, chloride channels capable of filtering glutamate, as well as Potassium (K+)-channel [2]. Glu attains α [3] and β [4] crystal forms and Cβ-CH2 show asymmetric 1H signal pattern in NMR spectra. Objectives: The current study was undertaken to understand the signal patterns of Cβ-CH2 in Glu of the smallest dipeptide, Glycylglutamic Acid (GlyGlu), as well as the order, and planarity of the amide bond in the molecule. Materials and Methods: NMR spectra of GlyGlu were measured in D2O to deduce 1H and 13C chemical shifts and coupling constants. GlyGlu was crystallized from MeOH and the structure was determined by single crystal X-ray diffraction techniques. Results: The sidechain of Glu in the dipeptide dissimilates the β form. The amino group of Gly (Glycine) is protonated and exhibits hydrogen bonding with the main chain carboxylate group of a symmetry-related Glu that is deprotonated in the crystal packing of GlyGlu. The deprotonated main chain carboxylate of Glu is also in hydrogen-bonding distance from the side chain carboxylic acid group that is in the protonated form of a symmetry-related Glu of the dipeptide. The Cβ-CH2 geminal protons on the side chain of Glu have different chemical shifts and splitting pattern in 1H NMR reflecting their dissymmetric environment. Conclusion: The results reported will be useful for monitoring changes that Glu and/or molecules in connection to Glu may undergo in in vivo, in situ, and in vitro conditions. This provides a valuable metric which will enable the examination of the metabolites relevant to the detection and diagnosis of disease or developmental conditions, as well as scrutinizing the effectiveness of treatment options.

KEYWORDS
Autism, Biomarker, Diabetes, Dipeptide, Structure, AGE, Derivatization

Cite This Paper in IEEE or APA Citation Styles
(a). IEEE Format:
[1] Amanda Hoff , Nigam Rath , John Lisko , Matthias Zeller , Ganesaratnam K. Balendiran , "Signature of Glycylglutamic Acid Structure," International Journal of Biochemistry and Biophysics, Vol. 9, No. 1, pp. 8 - 15, 2021. DOI: 10.13189/ijbb.2021.090102.

(b). APA Format:
Amanda Hoff , Nigam Rath , John Lisko , Matthias Zeller , Ganesaratnam K. Balendiran (2021). Signature of Glycylglutamic Acid Structure. International Journal of Biochemistry and Biophysics, 9(1), 8 - 15. DOI: 10.13189/ijbb.2021.090102.