scholarly journals Differentiating N-Terminal Aspartic and Isoaspartic Acid Residues in Peptides

2011 ◽  
Vol 83 (17) ◽  
pp. 6675-6682 ◽  
Author(s):  
Nadezda P. Sargaeva ◽  
Cheng Lin ◽  
Peter B. O’Connor
Keyword(s):  
Isoaspartic Acid

Unprecedented Occurrence of Isoaspartic Acid in a Plant Cyclopeptide

2012 ◽  
Vol 14 (2) ◽  
pp. 576-579 ◽  
Author(s):  
Damien Lacroix ◽  
Soizic Prado ◽  
Dennis Kamoga ◽  
John Kasenene ◽  
Séverine Zirah ◽  
...  
Keyword(s):  
Isoaspartic Acid

Differentiation and Semiquantitative Analysis of an Isoaspartic Acid in Human α-Crystallin by Postsource Decay in a Curved Field Reflectron

2010 ◽  
Vol 82 (15) ◽  
pp. 6384-6394 ◽  
Author(s):  
Yuzo Yamazaki ◽  
Norihiko Fujii ◽  
Yutaka Sadakane ◽  
Noriko Fujii
Keyword(s):  
Semiquantitative Analysis ◽  
Isoaspartic Acid ◽  
Postsource Decay

A critical assessment of force field accuracy against NMR data for cyclic peptides containing β-amino acids

2018 ◽  
Vol 20 (23) ◽  
pp. 15807-15816 ◽  
Author(s):  
C. Paissoni ◽  
F. Nardelli ◽  
S. Zanella ◽  
F. Curnis ◽  
L. Belvisi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Force Field ◽  
Cyclic Peptides ◽  
Force Fields ◽  
Critical Assessment ◽  
Isoaspartic Acid ◽  
Nmr Parameters ◽  
Nmr Data ◽  
Conformational Properties

A critical assessment of the reproducibility of NMR parameters of β amino acids pinpoints the major weaknesses of eight widely used force fields in reproducing the equilibrium conformational properties of highly constrained cyclic peptides containing isoAspartic acid.

scholarly journals Deamidated Human Triosephosphate Isomerase is a Promising Druggable Target

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1050
Author(s):  
Sergio Enríquez-Flores ◽  
Luis Antonio Flores-López ◽  
Itzhel García-Torres ◽  
Ignacio de la Mora-de la Mora ◽  
Nallely Cabrera ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Triosephosphate Isomerase ◽  
Noncovalent Interactions ◽  
Severe Disease ◽  
Selective Inhibition ◽  
Therapeutic Strategies ◽  
Glycolytic Enzyme ◽  
Enzyme Inactivation ◽  
Isoaspartic Acid

Therapeutic strategies for the treatment of any severe disease are based on the discovery and validation of druggable targets. The human genome encodes only 600–1500 targets for small-molecule drugs, but posttranslational modifications lead to a considerably larger druggable proteome. The spontaneous conversion of asparagine (Asn) residues to aspartic acid or isoaspartic acid is a frequent modification in proteins as part of the process called deamidation. Triosephosphate isomerase (TIM) is a glycolytic enzyme whose deamidation has been thoroughly studied, but the prospects of exploiting this phenomenon for drug design remain poorly understood. The purpose of this study is to demonstrate the properties of deamidated human TIM (HsTIM) as a selective molecular target. Using in silico prediction, in vitro analyses, and a bacterial model lacking the tim gene, this study analyzed the structural and functional differences between deamidated and nondeamidated HsTIM, which account for the efficacy of this protein as a druggable target. The highly increased permeability and loss of noncovalent interactions of deamidated TIM were found to play a central role in the process of selective enzyme inactivation and methylglyoxal production. This study elucidates the properties of deamidated HsTIM regarding its selective inhibition by thiol-reactive drugs and how these drugs can contribute to the development of cell-specific therapeutic strategies for a variety of diseases, such as COVID-19 and cancer.

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