Higher Order Structure in the Gas Phase Reflects Solution Structure

1998 ◽  
Vol 120 (18) ◽  
pp. 4542-4543 ◽  
Author(s):  
Joseph A. Loo ◽  
John X. He ◽  
Wayne L. Cody
Keyword(s):  
Gas Phase ◽  
Solution Structure ◽  
Higher Order ◽  
Order Structure

Characterization of nucleic acid higher order structure by gas-phase H/D exchange in a quadrupole-FT-ICR mass spectrometer

Biopolymers ◽  
2009 ◽  
Vol 91 (4) ◽  
pp. 256-264 ◽  
Author(s):  
Jingjie Mo ◽  
Gabrielle C. Todd ◽  
Kristina Håkansson
Keyword(s):  
Nucleic Acid ◽  
Gas Phase ◽  
Mass Spectrometer ◽  
Higher Order ◽  
Order Structure ◽  
Ft Icr

Macrocycles of Higher Ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Macrocycles of Higher ortho-Phenylenes: Assembly and Folding

2019 ◽  
Author(s):  
Zacharias Kinney ◽  
Viraj Kirinda ◽  
Scott Hartley
Keyword(s):  
Chemical Shift ◽  
Higher Order ◽  
Order Structure ◽  
Complex Geometries ◽  
Spatial Relationships ◽  
Predominant Species ◽  
Bite Angle ◽  
Direct Assembly

<p>Higher-order structure in abiotic foldamer systems represents an important but largely unrealized goal. As one approach to this challenge, covalent assembly can be used to assemble macrocycles with foldamer subunits in well-defined spatial relationships. Such systems have previously been shown to exhibit self-sorting, new folding motifs, and dynamic stereoisomerism, yet there remain important questions about the interplay between folding and macrocyclization and the effect of structural confinement on folding behavior. Here, we explore the dynamic covalent assembly of extended <i>ortho</i>-phenylenes (hexamer and decamer) with rod-shaped linkers. Characteristic <sup>1</sup>H chemical shift differences between cyclic and acyclic systems can be compared with computational conformer libraries to determine the folding states of the macrocycles. We show that the bite angle provides a measure of the fit of an <i>o</i>-phenylene conformer within a shape-persistent macrocycle, affecting both assembly and ultimate folding behavior. For the <i>o</i>-phenylene hexamer, the bite angle and conformer stability work synergistically to direct assembly toward triangular [3+3] macrocycles of well-folded oligomers. For the decamer, the energetic accessibility of conformers with small bite angles allows [2+2] macrocycles to be formed as the predominant species. In these systems, the <i>o</i>-phenylenes are forced into unusual folding states, preferentially adopting a backbone geometry with distinct helical blocks of opposite handedness. The results show that simple geometric restrictions can be used to direct foldamers toward increasingly complex geometries.</p>

Current Trends in Biotherapeutic Higher Order Structure Characterization by Irreversible Covalent Footprinting Mass Spectrometry

2019 ◽  
Vol 26 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Natalie K. Garcia ◽  
Galahad Deperalta ◽  
Aaron T. Wecksler
Keyword(s):  
Mass Spectrometry ◽  
Protein Structure ◽  
Protein Interactions ◽  
Quaternary Structure ◽  
Solvent Accessibility ◽  
Higher Order ◽  
Structure Characterization ◽  
Order Structure ◽  
Protein Footprinting ◽  
Wide Range

Background: Biotherapeutics, particularly monoclonal antibodies (mAbs), are a maturing class of drugs capable of treating a wide range of diseases. Therapeutic function and solutionstability are linked to the proper three-dimensional organization of the primary sequence into Higher Order Structure (HOS) as well as the timescales of protein motions (dynamics). Methods that directly monitor protein HOS and dynamics are important for mapping therapeutically relevant protein-protein interactions and assessing properly folded structures. Irreversible covalent protein footprinting Mass Spectrometry (MS) tools, such as site-specific amino acid labeling and hydroxyl radical footprinting are analytical techniques capable of monitoring the side chain solvent accessibility influenced by tertiary and quaternary structure. Here we discuss the methodology, examples of biotherapeutic applications, and the future directions of irreversible covalent protein footprinting MS in biotherapeutic research and development. Conclusion: Bottom-up mass spectrometry using irreversible labeling techniques provide valuable information for characterizing solution-phase protein structure. Examples range from epitope mapping and protein-ligand interactions, to probing challenging structures of membrane proteins. By paring these techniques with hydrogen-deuterium exchange, spectroscopic analysis, or static-phase structural data such as crystallography or electron microscopy, a comprehensive understanding of protein structure can be obtained.

Transdiagnostic dimensions in obsessive-compulsive and related disorders: associations with internalizing and externalizing symptoms

2020 ◽  
pp. 1-9
Author(s):  
Ivar Snorrason ◽  
Courtney Beard ◽  
Andrew D. Peckham ◽  
Thröstur Björgvinsson
Keyword(s):  
Internalizing Symptoms ◽  
Externalizing Symptoms ◽  
Higher Order ◽  
Order Structure ◽  
Obsessive Compulsive ◽  
Addictive Disorders ◽  
Compulsive Disorder ◽  
Alcohol Cravings ◽  
Internalizing And Externalizing ◽  
Internalizing And Externalizing Symptoms

Abstract Background Hierarchical structural models of psychopathology rarely extend to obsessive-compulsive spectrum disorders. The current study sought to examine the higher-order structure of the obsessive-compulsive and related disorders (OCRDs) in DSM-5: obsessive-compulsive disorder (OCD), hoarding disorder (HD), body dysmorphic disorder (BDD), trichotillomania (hair-pulling disorder; HPD) and excoriation (skin-picking) disorder (SPD). Methods Adult patients in a partial hospital program (N = 532) completed a dimensional measure of the five OCRDs. We used confirmatory factor analysis to identify the optimal model of the comorbidity structure. We then examined the associations between the transdiagnostic factors and internalizing and externalizing symptoms (i.e. depression, generalized anxiety, neuroticism, and drug/alcohol cravings). Results The best fitting model included two correlated higher-order factors: an obsessions-compulsions (OC) factor (OCD, BDD, and HD), and a body-focused repetitive behavior (BFRB) factor (HPD and SPD). The OC factor, not the BFRB factor, had unique associations with internalizing symptoms (standardized effects = 0.42–0.66) and the BFRB factor, not the OC factor, had small marginally significant unique association with drug/alcohol cravings (standardized effect = 0.22, p = 0.088). Conclusions The results mirror findings from twin research and indicate that OCD, BDD, and HD share liability that is significantly associated with internalizing symptoms, but this liability may be relatively less important for BFRBs. Further research is needed to better examine the associations between BFRBs and addictive disorders.

scholarly journals Unravelling a Direct Role for Polysaccharide β-Strands in the Higher Order Structure of Physical Hydrogels

2017 ◽  
Vol 56 (16) ◽  
pp. 4603-4607 ◽  
Author(s):  
Anja Rüther ◽  
Aurelien Forget ◽  
Anjan Roy ◽  
Carolina Carballo ◽  
Florian Mießmer ◽  
...  
Keyword(s):  
Higher Order ◽  
Order Structure ◽  
Direct Role
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