A 2,7-diamino-1,4,8-triazanaphthalene derivative selectively binds to cytosine bulge DNA only at a weakly acidic pH

2017 ◽  
Vol 15 (6) ◽  
pp. 1313-1316 ◽  
Author(s):  
H. Aikawa ◽  
A. Yano ◽  
K. Nakatani
Keyword(s):  
Acidic Ph ◽  
Dna Duplex ◽  
Ph Profile ◽  
Selective Binding ◽  
Absorption Change ◽  
Bulge Dna ◽  
Acidic Conditions

2,7-Diamino-1,4,8-triazanaphthalene (azaDANP) shows selective binding to a cytosine bulge DNA duplex under weakly acidic conditions, and the absorption change of azaDANP on binding to the target is very sensitive to environmental pH with a bell-shaped absorption–pH profile.

scholarly journals Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

2020 ◽  
Vol 14 (1) ◽  
pp. 22
Author(s):  
Kenji Tsukigawa ◽  
Shuhei Imoto ◽  
Keishi Yamasaki ◽  
Koji Nishi ◽  
Toshihiko Tsutsumi ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Coupling Reaction ◽  
Synthetic Polymer ◽  
Ph Sensitive ◽  
Acidic Ph ◽  
Polymer Conjugate ◽  
Acidic Conditions

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development.

scholarly journals Heterocyclic boronic acids display sialic acid selective binding in a hypoxic tumor relevant acidic environment

2017 ◽  
Vol 8 (9) ◽  
pp. 6165-6170 ◽  
Author(s):  
A. Matsumoto ◽  
A. J. Stephenson-Brown ◽  
T. Khan ◽  
T. Miyazawa ◽  
H. Cabral ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Boronic Acids ◽  
Sialic Acids ◽  
Strong Interactions ◽  
Acidic Ph ◽  
Acidic Environment ◽  
Selective Binding ◽  
High Affinity ◽  
Ph Conditions ◽  
Hypoxic Tumor

A group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids are described, with strong interactions under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment.

Search for DNA Repair Inhibitors:  Selective Binding of Nucleic Bases−Acridine Conjugates to a DNA Duplex Containing an Abasic Site†

1997 ◽  
Vol 40 (21) ◽  
pp. 3346-3352 ◽  
Author(s):  
Nathalie Berthet ◽  
Jean-François Constant ◽  
Martine Demeunynck ◽  
Pierre Michon ◽  
Jean Lhomme
Keyword(s):  
Dna Repair ◽  
Abasic Site ◽  
Dna Duplex ◽  
Selective Binding ◽  
Nucleic Bases ◽  
Dna Repair Inhibitors

Shape-Selective Binding of Geometrically-Constrainedbis-Distamycins to a DNA Duplex and a Model Okazaki Fragment of Identical Sequence

2000 ◽  
Vol 19 (8) ◽  
pp. 1365-1379 ◽  
Author(s):  
William H. Gmeiner ◽  
Wei Cui ◽  
Sanjay Sharma ◽  
Ana Maria Soto ◽  
Luis A. Marky ◽  
...  
Keyword(s):  
Dna Duplex ◽  
Selective Binding ◽  
Okazaki Fragment ◽  
Shape Selective

Tensile, physical, and microstructure properties of glycine treated cotton fibers

2017 ◽  
Vol 88 (12) ◽  
pp. 1356-1366 ◽  
Author(s):  
Rechana Remadevi ◽  
Stuart Gordon ◽  
Xungai Wang ◽  
Rangam Rajkhowa
Keyword(s):  
Linear Density ◽  
Cotton Fibers ◽  
Acidic Ph ◽  
Alkaline Ph ◽  
X Ray Diffraction ◽  
Density Measurements ◽  
X Ray ◽  
Acidic Conditions ◽  
Improved Strain ◽  
Control Samples

In this paper, the effect of aqueous glycine treatments at different pH on the tensile properties of cotton fibers is reported. The effects on linear density and X-ray diffraction crystallinity were also evaluated. Glycine treated fibers at alkaline pH (i.e. at pH 11) produced fibers with higher linear density than control (untreated) and glycine treatments at acidic pH. The same treatment also increased strain values in cotton fibers by as much as 36%. Interestingly, similar changes in strain were observed under acidic conditions, especially at pH4, although the changes were smaller. Specific stress values normalized by the linear density measurements were not significantly different from control samples. The results of this research demonstrated improved strain properties of cotton fibers after aqueous glycine treatment at suitable conditions.

Abstract 1548: Acidic pH selective binding of VISTA to PSGL-1 and anti-tumor activity of combined VISTA and PD-1 blockade

2019 ◽  
Author(s):  
Robert J. Johnston ◽  
Linhui Julie Su ◽  
Jason Pinckney ◽  
David Critton ◽  
Arathi Krishnakumar ◽  
...  
Keyword(s):  
Acidic Ph ◽  
Selective Binding ◽  
Anti Tumor Activity

scholarly journals Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB2-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

2019 ◽  
Vol 15 ◽  
pp. 1925-1932 ◽  
Author(s):  
Yang Bai ◽  
Cai-ping Liu ◽  
Di Chen ◽  
Long-hai Zhuo ◽  
Huai-tian Bu ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Self Assembly ◽  
Controlled Drug Delivery ◽  
Transition Process ◽  
Hydrodynamic Diameter ◽  
Cancer Cell Proliferation ◽  
Acidic Ph ◽  
Stimuli Responsive ◽  
Amphiphilic Molecules ◽  
Acidic Conditions

Although stimuli-responsive supramolecular self-assemblies have been constructed, the controlled drug delivery induced by morphology transitions of these supramolecular self-assemblies on the basis of host–guest-conjugated monomers (HGCMs) are few reported. In this paper, the self-assembly behaviors of AB2-type HGCMs, e.g., β-cyclodextrin-benzimidazole2 (β-CD-BM2), were investigated at neutral and acidic pH conditions, respectively. Specifically, β-CD-BM2 first self-assembled into fan-shaped supramolecular self-assemblies with a hydrodynamic diameter of 163 nm at neutral pH, whereas they were further dissociated into spherical supramolecular self-assemblies with a size of 52 nm under acidic conditions. This morphology transition process was utilized to conduct a two-stage DOX delivery under neutral and acidic pH. Basic cell experiments demonstrated that the drug-loaded β-CD-BM2-based supramolecular self-assemblies with varied morphology could inhibit cancer cell proliferation, indicating their potential application in the field of drug delivery.

Troponin I isoforms and differential effects of acidic pH on soleus and cardiac myofilaments

1995 ◽  
Vol 268 (2) ◽  
pp. C323-C330 ◽  
Author(s):  
J. Wattanapermpool ◽  
P. J. Reiser ◽  
R. J. Solaro
Keyword(s):  
Troponin I ◽  
Troponin C ◽  
Binary Complex ◽  
Acidic Ph ◽  
Differential Effects ◽  
Adult Rat ◽  
Effects Of Ph ◽  
Isoform Switching ◽  
Acidic Conditions ◽  
Tension Generation

Differences in pH sensitivity of tension generation between developing and adult cardiac myofilaments, which contain the same isoform of troponin C (TnC), have been proposed to be due to troponin I (TnI) isoform switching from the slow skeletal (ss) to cardiac (c) TnI isoforms (21). We investigated the effects of acidic pH on Ca(2+)-activation of force in chemically skinned preparations of adult rat trabeculae and single soleus fibers that also share the same TnC isoform. Compared with the soleus fibers, trabeculae demonstrated a greater suppression of tension and a rightward shift in pCa50 (-log half-maximally activating molar Ca2+ concentration) when pH was decreased from 7.0 to 6.2. The pH-induced shift in pCa50 in soleus fibers did not change with sarcomere length. Troponin subunit interactions were also investigated, using cardiac troponin C (cTnCIA) labeled with a fluorescent probe, 2-(4'-iodoacetamidoanilino)-naphthalene-6-sulfonic acid. Under acidic conditions, cTnCIA demonstrated a decrease in Ca(2+)-affinity. This decrease was amplified both in the binary complex cTnCIA-cTnI and in the complex cTnCIA-cTnI-cTnT-tropomyosin to the same extent. In contrast, substitution of ssTnI for cTnI in these complexes produced the same decrease in Ca2+ affinity in response to acidic pH as cTnCIA alone. These results support our hypothesis that differential effects of pH on tension generation and Ca2+ sensitivity between soleus fibers and trabeculae are due to the presence of different isoforms of TnI.

scholarly journals Acidification of Rat TRPV1 Alters the Kinetics of Capsaicin Responses

2005 ◽  
Vol 1 ◽  
pp. 1744-8069-1-28 ◽  
Author(s):  
Torben R Neelands ◽  
Michael F Jarvis ◽  
Ping Han ◽  
Connie R Faltynek ◽  
Carol S Surowy
Keyword(s):  
Acidic Ph ◽  
Hek 293 ◽  
Deactivation Rate ◽  
Vanilloid Receptor 1 ◽  
293 Cells ◽  
Activation Rate ◽  
Current Activation ◽  
Acidic Conditions ◽  
Tissue Acidosis ◽  
Trpv1 Antagonist

TRPV1 (vanilloid receptor 1) receptors are activated by a variety of ligands such as capsaicin, as well as by acidic conditions and temperatures above 42°C. These activators can enhance the potency of one another, shifting the activation curve for TRPV1 to the left. In this study, for example, we observed an approximately 10-fold shift in the capsaicin EC50 (640 nM to 45 nM) for rat TRPV1 receptors expressed in HEK-293 cells when the pH was lowered from 7.4 to 5.5. To investigate potential causes for this shift in capsaicin potency, the rates of current activation and deactivation of whole-cell currents were measured in individual cells exposed to treatments of pH 5.5, 1 μM capsaicin or in combination. Acidic pH was found to both increase the activation rate and decrease the deactivation rate of capsaicin-activated currents providing a possible mechanism for the enhanced potency of capsaicin under acidic conditions. Utilizing a paired-pulse protocol, acidic pH slowed the capsaicin deactivation rate and was readily reversible. Moreover, the effect could occur under modestly acidic conditions (pH 6.5) that did not directly activate TRPV1. When TRPV1 was maximally activated by capsaicin and acidic pH, the apparent affinity of the novel and selective capsaicin-site competitive TRPV1 antagonist, A-425619, was reduced ∼35 fold. This shift was overcome by reducing the capsaicin concentration co-applied with acidic pH. Since inflammation is associated with tissue acidosis, these findings enhance understanding of TRPV1 receptor responses in inflammatory pain where tissue acidosis is prevalent.

scholarly journals Iron release from haemosiderin and production of iron-catalysed hydroxyl radicals in vitro

1988 ◽  
Vol 250 (2) ◽  
pp. 589-595 ◽  
Author(s):  
M Ozaki ◽  
T Kawabata ◽  
M Awai
Keyword(s):  
Hydroxyl Radicals ◽  
Ph Dependence ◽  
Weight Ratio ◽  
Acidic Ph ◽  
Iron Release ◽  
Physiological Conditions ◽  
Radical Production ◽  
Acidic Conditions ◽  
Neutral Conditions

Isolated haemosiderin contained iron and nitrogen in a weight ratio of 6.75, with phosphorus and no detectable haem. Considerably more iron was released from haemosiderin under acidic conditions than under neutral conditions in the presence of ascorbate, nitrilotriacetate or dithionite. Unlike the situation with ascorbate, chelators such as citrate, ADP or succinate induced the release of only some iron, with almost no pH-dependence. Dehydroascorbate (the oxidized form of ascorbate with no reducing capacity) behaved like citrate, ADP, succinate or desferal, rather than like ascorbate itself, in releasing iron. GSH had less effect on the release of iron than these chelators, but in the presence of a small amount of chelator the release of iron increased, especially under acidic conditions. Thus reduction, chelation and pH were all found to be important factors involved in the release of iron from haemosiderin. Investigation by e.p.r. of hydroxyl-radical production by the released iron showed high radical productivity at an acidic pH. However, at a physiological pH, almost no radical formation was detected, except in the presence of nitrilotriacetate. These findings suggested that, under physiological conditions, haemosiderin was not an effective iron donor and was almost not involved in radical production. Under acidic conditions, however, such as in inflammation, hypoxia and in a lysosomal milieu, it could possibly be an iron donor and is thought to be implicated in radical production and tissue damage in iron-overloaded conditions.

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