Unusual pH-Dependent Polarity Changes in PAMAM Dendrimers:  Evidence for pH-Responsive Conformational Changes

2000 ◽  
Vol 33 (25) ◽  
pp. 9169-9172 ◽  
Author(s):  
Wei Chen ◽  
Donald A. Tomalia ◽  
James L. Thomas
Keyword(s):  
Conformational Changes ◽  
Pamam Dendrimers ◽  
Ph Responsive ◽  
Ph Dependent

PAMAM Dendrimers Undergo pH Responsive Conformational Changes without Swelling

2009 ◽  
Vol 131 (8) ◽  
pp. 2798-2799 ◽  
Author(s):  
Yi Liu ◽  
Vyacheslav S. Bryantsev ◽  
Mamadou S. Diallo ◽  
William A. Goddard III
Keyword(s):  
Conformational Changes ◽  
Pamam Dendrimers ◽  
Ph Responsive

pH-Dependent Thermal Stability of Vibrio cholerae L-asparaginase

2019 ◽  
Vol 26 (10) ◽  
pp. 743-750 ◽  
Author(s):  
Remya Radha ◽  
Sathyanarayana N. Gummadi
Keyword(s):  
Vibrio Cholerae ◽  
Conformational Changes ◽  
Kinetic Studies ◽  
Structural Features ◽  
Structure Stability ◽  
Kcal Mole ◽  
Scanning Calorimetry ◽  
Wide Range ◽  
Ph Dependent ◽  
Ph Range

Background:pH is one of the decisive macromolecular properties of proteins that significantly affects enzyme structure, stability and reaction rate. Change in pH may protonate or deprotonate the side group of aminoacid residues in the protein, thereby resulting in changes in chemical and structural features. Hence studies on the kinetics of enzyme deactivation by pH are important for assessing the bio-functionality of industrial enzymes. L-asparaginase is one such important enzyme that has potent applications in cancer therapy and food industry.Objective:The objective of the study is to understand and analyze the influence of pH on deactivation and stability of Vibrio cholerae L-asparaginase.Methods:Kinetic studies were conducted to analyze the effect of pH on stability and deactivation of Vibrio cholerae L-asparaginase. Circular Dichroism (CD) and Differential Scanning Calorimetry (DSC) studies have been carried out to understand the pH-dependent conformational changes in the secondary structure of V. cholerae L-asparaginase.Results:The enzyme was found to be least stable at extreme acidic conditions (pH< 4.5) and exhibited a gradual increase in melting temperature from 40 to 81 °C within pH range of 4.0 to 7.0. Thermodynamic properties of protein were estimated and at pH 7.0 the protein exhibited ΔG37of 26.31 kcal mole-1, ΔH of 204.27 kcal mole-1 and ΔS of 574.06 cal mole-1 K-1.Conclusion:The stability and thermodynamic analysis revealed that V. cholerae L-asparaginase was highly stable over a wide range of pH, with the highest stability in the pH range of 5.0–7.0.

scholarly journals Correlation of membrane protein conformational and functional dynamics

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Raghavendar Reddy Sanganna Gari ◽  
Joel José Montalvo‐Acosta ◽  
George R. Heath ◽  
Yining Jiang ◽  
Xiaolong Gao ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Conformational Changes ◽  
Single Channel ◽  
Conformational Dynamics ◽  
Md Simulations ◽  
High Temporal Resolution ◽  
Dependent Manner ◽  
Functional Dynamics ◽  
Ph Dependent ◽  
Open States

AbstractConformational changes in ion channels lead to gating of an ion-conductive pore. Ion flux has been measured with high temporal resolution by single-channel electrophysiology for decades. However, correlation between functional and conformational dynamics remained difficult, lacking experimental techniques to monitor sub-millisecond conformational changes. Here, we use the outer membrane protein G (OmpG) as a model system where loop-6 opens and closes the β-barrel pore like a lid in a pH-dependent manner. Functionally, single-channel electrophysiology shows that while closed states are favored at acidic pH and open states are favored at physiological pH, both states coexist and rapidly interchange in all conditions. Using HS-AFM height spectroscopy (HS-AFM-HS), we monitor sub-millisecond loop-6 conformational dynamics, and compare them to the functional dynamics from single-channel recordings, while MD simulations provide atomistic details and energy landscapes of the pH-dependent loop-6 fluctuations. HS-AFM-HS offers new opportunities to analyze conformational dynamics at timescales of domain and loop fluctuations.

scholarly journals pH-responsive antibodies for therapeutic applications

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Tomasz Klaus ◽  
Sameer Deshmukh
Keyword(s):  
Drug Delivery ◽  
Treatment Outcome ◽  
Tumor Microenvironment ◽  
Dependent Manner ◽  
Therapeutic Antibodies ◽  
Ph Responsive ◽  
Biologic Drugs ◽  
Car T ◽  
Ph Dependent ◽  
The Brain

AbstractTherapeutic antibodies are instrumental in improving the treatment outcome for certain disease conditions. However, to enhance their efficacy and specificity, many efforts are continuously made. One of the approaches that are increasingly explored in this field are pH-responsive antibodies capable of binding target antigens in a pH-dependent manner. We reviewed suitability and examples of these antibodies that are functionally modulated by the tumor microenvironment. Provided in this review is an update about antigens targeted by pH-responsive, sweeping, and recycling antibodies. Applicability of the pH-responsive antibodies in the engineering of chimeric antigen receptor T-cells (CAR-T) and in improving drug delivery to the brain by the enhanced crossing of the blood–brain barrier is also discussed. The pH-responsive antibodies possess strong treatment potential. They emerge as next-generation programmable engineered biologic drugs that are active only within the targeted biological space. Thus, they are valuable in targeting acidified tumor microenvironment because of improved spatial persistence and reduced on-target off-tumor toxicities. We predict that the programmable pH-dependent antibodies become powerful tools in therapies of cancer.

Glycan chip based on structure switchable DNA linker for on-chip biosynthesis of cancer-associated complex glycans

2021 ◽  
Author(s):  
Hye Ryoung Heo ◽  
Kye Il Joo ◽  
Jeong Hyun Seo ◽  
Chang Sup Kim ◽  
Hyung Joon Cha
Keyword(s):  
Breast Cancer Cells ◽  
Enzymatic Reactions ◽  
Dependent Manner ◽  
Ph Responsive ◽  
Quantitative Analyses ◽  
Ph Dependent ◽  
Complex Glycans ◽  
On Chip ◽  
Complex Glycan ◽  
Mcf 7

Abstract On-chip glycan biosynthesis is an effective strategy for preparing useful complex glycan sources and for preparing glycan-involved applications simultaneously. However, current methods have some limitations when analyzing biosynthesized glycans and optimizing enzymatic reactions, which could result in undefined glycan structures on a surface, leading to unequal and unreliable results. In this work, a novel glycan chip was developed by introducing a pH-responsive i-motif DNA linker to control the immobilization and isolation of glycans on chip surfaces in a pH-dependent manner. On-chip enzymatic glycosylations were optimized for uniform biosynthesis of cancer-associated Globo H hexasaccharide and its related complex glycans through stepwise quantitative analyses of isolated products from the surface. Successful interaction analyses of the anti-Globo H antibody and MCF-7 breast cancer cells with on-chip biosynthesized Globo H-related glycans demonstrated the feasibility of the structure-switchable DNA linker-based glycan chip platform for on-chip complex glycan biosynthesis and glycan-involved applications.

scholarly journals pH-Dependent Conformational Changes in Proteins and Their Effect on Experimental pKas: The Case of Nitrophorin 4

2012 ◽  
Vol 8 (11) ◽  
pp. e1002761 ◽  
Author(s):  
Natali V. Di Russo ◽  
Dario A. Estrin ◽  
Marcelo A. Martí ◽  
Adrian E. Roitberg
Keyword(s):  
Conformational Changes ◽  
Nitrophorin 4 ◽  
Ph Dependent

Spatiotemporal control over the co-conformational switching in pH-responsive flavylium-based multistate pseudorotaxanes

2015 ◽  
Vol 185 ◽  
pp. 361-379 ◽  
Author(s):  
Ana Marta Diniz ◽  
Nuno Basílio ◽  
Hugo Cruz ◽  
Fernando Pina ◽  
A. Jorge Parola
Keyword(s):  
Molecular Organization ◽  
Present System ◽  
Spectroscopic Techniques ◽  
Ph Responsive ◽  
Conformational Switching ◽  
Ph Values ◽  
Stable Species ◽  
Ph Dependent ◽  
Spatiotemporal Control ◽  
Kinetics Of

A multistate molecular dyad containing flavylium and viologen units was synthesized and the pH dependent thermodynamics of the network completely characterized by a variety of spectroscopic techniques such as NMR, UV-vis and stopped-flow. The flavylium cation is only stable at acidic pH values. Above pH ≈ 5 the hydration of the flavylium leads to the formation of the hemiketal followed by ring-opening tautomerization to give the cis-chalcone. Finally, this last species isomerizes to give the trans-chalcone. For the present system only the flavylium cation and the trans-chalcone species could be detected as being thermodynamically stable. The hemiketal and the cis-chalcone are kinetic intermediates with negligible concentrations at the equilibrium. All stable species of the network were found to form 1 : 1 and 2 : 1 host : guest complexes with cucurbit[7]uril (CB7) with association constants in the ranges 105–108 M−1 and 103–104 M−1, respectively. The 1 : 1 complexes were particularly interesting to devise pH responsive bistable pseudorotaxanes: at basic pH values (≈12) the flavylium cation interconverts into the deprotonated trans-chalcone in a few minutes and under these conditions the CB7 wheel was found to be located around the viologen unit. A decrease in pH to values around 1 regenerates the flavylium cation in seconds and the macrocycle is translocated to the middle of the axle. On the other hand, if the pH is decreased to 6, the deprotonated trans-chalcone is neutralized to give a metastable species that evolves to the thermodynamically stable flavylium cation in ca. 20 hours. By taking advantage of the pH-dependent kinetics of the trans-chalcone/flavylium interconversion, spatiotemporal control of the molecular organization in pseudorotaxane systems can be achieved.

scholarly journals pH-Dependent Conformational Changes of Concanavalin A

1971 ◽  
Vol 68 (9) ◽  
pp. 2173-2176 ◽  
Author(s):  
R. Zand ◽  
B. B. L. Agrawal ◽  
I. J. Goldstein
Keyword(s):  
Conformational Changes ◽  
Concanavalin A ◽  
Ph Dependent
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