scholarly journals Shape Effects of Peptide Amphiphile Micelles for Targeting Monocytes

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2786 ◽  
Author(s):  
Johan Joo ◽  
Christopher Poon ◽  
Sang Yoo ◽  
Eun Chung
Keyword(s):  
Cancer Progression ◽  
Peptide Amphiphile ◽  
Monocyte Chemoattractant Protein 1 ◽  
Hydrophobic Moiety ◽  
Vitro Binding ◽  
Wide Range ◽  
Shape Effects ◽  
Multivalent Display ◽  
In Vitro Binding Assay

Peptide amphiphile micelles (PAMs) are a nanoparticle platform that have gained popularity for their targeting versatility in a wide range of disease models. An important aspect of micelle design is considering the type of hydrophobic moiety used to synthesize the PAM, which can act as a contributing factor regarding their morphology and targeting capabilities. To delineate and compare the characteristics of spherical and cylindrical micelles, we incorporated the monocyte-targeting chemokine, monocyte chemoattractant protein-1 (MCP-1), into our micelles (MCP-1 PAMs). We report that both shapes of nanoparticles were biocompatible with monocytes and enhanced the secondary structure of the MCP-1 peptide, thereby improving the ability of the micelles to mimic the native MCP-1 protein structure. As a result, both shapes of MCP-1 PAMs effectively targeted monocytes in an in vitro binding assay with murine monocytes. Interestingly, cylindrical PAMs showed a greater ability to attract monocytes compared to spherical PAMs in a chemotaxis assay. However, the surface area, the multivalent display of peptides, and the zeta potential of PAMs may also influence their biomimetic properties. Herein, we introduce variations in the methods of PAM synthesis and discuss the differences in PAM characteristics that can impact the recruitment of monocytes, a process associated with disease and cancer progression.

scholarly journals The Ras-related protein R-ras interacts directly with Raf-1 in a GTP-dependent manner

1994 ◽  
Vol 300 (2) ◽  
pp. 303-307 ◽  
Author(s):  
M Spaargaren ◽  
G A Martin ◽  
F McCormick ◽  
M J Fernandez-Sarabia ◽  
J R Bischoff
Keyword(s):  
Amino Acids ◽  
Small Gtpases ◽  
Dependent Manner ◽  
Downstream Effector ◽  
Yeast Two Hybrid System ◽  
Vitro Binding ◽  
Ras Family ◽  
In Vitro Binding Assay ◽  
Two Hybrid

R-ras is a member of the ras family of small GTPases that associates with the apoptosis-suppressing proto-oncogene product Bcl-2. Using the yeast two-hybrid system we provide evidence for an interaction between R-ras and the Raf-1 kinase. This interaction requires only the N-terminal regulatory domain (amino acids 1-256) of Raf-1, and is observed with both the wild type and a constitutively active R-ras mutant, but not with a deletion mutant that lacks the potential effector domain or a mutant of R-ras impaired for GTP binding. Moreover, using an in vitro binding assay we show a direct GTP-dependent interaction of purified R-ras with a purified Raf-1 fragment corresponding to the proposed 81-amino-acid H-Ras-binding domain of Raf-1 (amino acids 51-131). Taken together, these data indicate that R-ras may exert its biological effect by means of modulating the activity of the Raf-1 kinase as its direct downstream effector.

An in vitro binding assay which differentiates benzodiazepine ‘agonists’ and ‘antagonists’

1982 ◽  
Vol 78 (1) ◽  
pp. 133-136 ◽  
Author(s):  
Phil Skolnick ◽  
Margaret M. Schweri ◽  
Evan F. Williams ◽  
Victoria Y. Moncada ◽  
Steven M. Paul
Keyword(s):  
Binding Assay ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
In Vitro Binding Assay

Changes in gonadotrophin binding to rat ovaries during sexual maturation

1983 ◽  
Vol 103 (3) ◽  
pp. 413-419 ◽  
Author(s):  
J. Th. J. Uilenbroek ◽  
R. van der Linden
Keyword(s):  
Granulosa Cells ◽  
Sexual Maturation ◽  
Specific Binding ◽  
Interstitial Tissue ◽  
Uterine Weight ◽  
Thecal Cells ◽  
Vitro Binding ◽  
In Vitro Binding Assay ◽  
Ovulatory Follicles

Abstract. Changes in LH and FSH binding to rat ovaries during sexual maturation were measured by in vitro binding assay and autoradiography. Ovaries were obtained from rats at various ages ranging from 5 till 35 days of age. Animals older than 35 days of age were classified in three groups: anoestrus (uterine weight below 60 mg), early pro-oestrus (uterine weight 60–120 mg) and pro-oestrus (uterus distended with fluid). Measurements were made of specific binding of radioiodinated hCG and rFSH to ovarian homogenates (day 5–35) and to granulosa cells isolated from the largest follicles (day 35–pro-oestrus). The earliest age at which specific hCG and FSH binding could be demonstrated was day 11. Thereafter hCG binding to ovarian homogenates, expressed in cpm/μg DNA, increased with age. Specific binding of hCG to granulosa cells increased from 1000 cpm/μg DNA at day 35 to 4000 cpm/μg DNA at pro-oestrus. FSH binding to ovarian homogenates increased till day 21 and remained fairly constant thereafter. Autoradiography revealed the presence of hCG binding to interstitial tissue and thecal cells. hCG binding to granulosa cells was only found in large pre-ovulatory follicles present at early pro-oestrus and pro-oestrus. FSH binding was observed to granulosa cells of all types of follicles, but not to interstitial and thecal cells. The results demonstrate that during sexual maturation FSH binding to granulosa cells remains constant, whereas LH binding to interstitium and theca and ultimately to granulosa cells increases with age suggesting an increased responsiveness of the ovaries to LH.

scholarly journals Repression of Wnt/β-catenin signaling by SOX9 and Mastermind-like transcriptional coactivator 2

2021 ◽  
Vol 7 (8) ◽  
pp. eabe0849
Author(s):  
Abhishek Sinha ◽  
Vinson B. Fan ◽  
Aravinda-Bharathi Ramakrishnan ◽  
Nicole Engelhardt ◽  
Jennifer Kennell ◽  
...  
Keyword(s):  
Wnt Pathway ◽  
Binding Assay ◽  
Mammalian Cell Culture ◽  
Transcriptional Coactivator ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Direct Binding ◽  
In Vitro Binding Assay ◽  
Potent Antagonist

Wnt/β-catenin signaling requires inhibition of a multiprotein destruction complex that targets β-catenin for proteasomal degradation. SOX9 is a potent antagonist of the Wnt pathway and has been proposed to act through direct binding to β-catenin or the β-catenin destruction complex. Here, we demonstrate that SOX9 promotes turnover of β-catenin in mammalian cell culture, but this occurs independently of the destruction complex and the proteasome. This activity requires SOX9’s ability to activate transcription. Transcriptome analysis revealed that SOX9 induces the expression of the Notch coactivator Mastermind-like transcriptional activator 2 (MAML2), which is required for SOX9-dependent Wnt/β-catenin antagonism. MAML2 promotes β-catenin turnover independently of Notch signaling, and MAML2 appears to associate directly with β-catenin in an in vitro binding assay. This work defines a previously unidentified pathway that promotes β-catenin degradation, acting in parallel to established mechanisms. SOX9 uses this pathway to restrict Wnt/β-catenin signaling.

Matrixmetalloproteinase Inhibitors: Promising Therapeutic Targets Against Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Vibha Rani ◽  
Dhananjay Yadav ◽  
Neha Atale
Keyword(s):  
Clinical Trials ◽  
Tumor Progression ◽  
Cancer Progression ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Mmp Inhibitors ◽  
Cellular Environment ◽  
Wide Range

Background: Cancer is a wide range cellular level disease that occurs when cells go through uncontrolled division and growth. The mechanisms by which the cells undergo metastasis are complex and involve many interactions between the tumor cells and their cellular environment. Matrix metalloproteinases (MMPs) have been found to over-express at various stages of tumor progression and their inhibition using MMP inhibitors has been a subject of potential therapy against cancer. Objective: This review discusses recent research in MMP inhibitors (MMPI) used for preventing tumor progression. Methods: In this review, we explored the role of MMPs in cancer progression and summarized the current developments in MMPIs, their role in cancer suppression in in vitro and in vivo studies and their evaluation in clinical trials from the current research data. Results: MMPIs have shown to be very successful in in vitro models, cell lines and in some in vivo studies. Unfortunately, their efficacy in clinical trials has been found to be hit and miss. Recent studies have shown that the novel delivery approaches of MMP inhibitors may enhance their therapeutic effects towards the prevention of cancer. Conclusion: In this review, we presented different MMP inhibitors, their performance at different stages of models - in vitro, in vivo, small animal models and eventually clinical trials. We provide newer methods of MMPI delivery that may be better targeted to suppress only specific MMPs and avoid toxic side-effects in healthy cells.

scholarly journals Human ornithine decarboxylase paralogue (ODCp) is an antizyme inhibitor but not an arginine decarboxylase

2007 ◽  
Vol 409 (1) ◽  
pp. 187-192 ◽  
Author(s):  
Kristiina Kanerva ◽  
Laura T. Mäkitie ◽  
Anna Pelander ◽  
Marja Heiskala ◽  
Leif C. Andersson
Keyword(s):  
Ornithine Decarboxylase ◽  
Arginine Decarboxylase ◽  
Polyamine Biosynthesis ◽  
Vitro Binding ◽  
In Vitro Binding Assay ◽  
Rate Limiting ◽  
Two Hybrid ◽  
Hybrid Screening

ODC (ornithine decarboxylase), the rate-limiting enzyme in polyamine biosynthesis, is regulated by specific inhibitors, AZs (antizymes), which in turn are inhibited by AZI (AZ inhibitor). We originally identified and cloned the cDNA for a novel human ODC-like protein called ODCp (ODC paralogue). Since ODCp was devoid of ODC catalytic activity, we proposed that ODCp is a novel form of AZI. ODCp has subsequently been suggested to function either as mammalian ADC (arginine decarboxylase) or as AZI in mice. Here, we report that human ODCp is a novel AZI (AZIN2). By using yeast two-hybrid screening and in vitro binding assay, we show that ODCp binds AZ1–3. Measurements of the ODC activity and ODC degradation assay reveal that ODCp inhibits AZ1 function as efficiently as AZI both in vitro and in vivo. We further demonstrate that the degradation of ODCp is ubiquitin-dependent and AZ1-independent similar to the degradation of AZI. We also show that human ODCp has no intrinsic ADC activity.

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