Unknown

Dataset Information

0

Synthesis and Evaluation of Non-Hydrolyzable Phospho-Lysine Peptide Mimics.


ABSTRACT: The intrinsic lability of the phosphoramidate P-N bond in phosphorylated histidine (pHis), arginine (pHis) and lysine (pLys) residues is a significant challenge for the investigation of these post-translational modifications (PTMs), which gained attention rather recently. While stable mimics of pHis and pArg have contributed to study protein substrate interactions or to generate antibodies for enrichment as well as detection, no such analogue has been reported yet for pLys. This work reports the synthesis and evaluation of two pLys mimics, a phosphonate and a phosphate derivative, which can easily be incorporated into peptides using standard fluorenyl-methyloxycarbonyl- (Fmoc-)based solid-phase peptide synthesis (SPPS). In order to compare the biophysical properties of natural pLys with our synthetic mimics, the pKa values of pLys and analogues were determined in titration experiments applying nuclear magnetic resonance (NMR) spectroscopy in small model peptides. These results were used to compute electrostatic potential (ESP) surfaces obtained after molecular geometry optimization. These findings indicate the potential of the designed non-hydrolyzable, phosphonate-based mimic for pLys in various proteomic approaches.

SUBMITTER: Hauser A 

PROVIDER: S-EPMC7898648 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Synthesis and Evaluation of Non-Hydrolyzable Phospho-Lysine Peptide Mimics.

Hauser Anett A   Poulou Eleftheria E   Müller Fabian F   Schmieder Peter P   Hackenberger Christian P R CPR  

Chemistry (Weinheim an der Bergstrasse, Germany) 20201207 7


The intrinsic lability of the phosphoramidate P-N bond in phosphorylated histidine (pHis), arginine (pHis) and lysine (pLys) residues is a significant challenge for the investigation of these post-translational modifications (PTMs), which gained attention rather recently. While stable mimics of pHis and pArg have contributed to study protein substrate interactions or to generate antibodies for enrichment as well as detection, no such analogue has been reported yet for pLys. This work reports the  ...[more]

Similar Datasets

| S-EPMC4027766 | biostudies-literature
| S-EPMC7555970 | biostudies-literature
| S-EPMC6555766 | biostudies-literature
| S-EPMC7024368 | biostudies-literature
| S-EPMC3654864 | biostudies-literature
| S-EPMC5392768 | biostudies-literature
| S-EPMC4206410 | biostudies-literature
| S-EPMC4360154 | biostudies-literature
| S-EPMC3586539 | biostudies-literature
| S-EPMC1693819 | biostudies-literature