Synthesis, DNA binding and anti-leukemic activity of an aminoacyl nucleolipid

Patel, Pradeepkumar; Hanawa, Emi; Yadav, Reeta; Samuni, Uri; Marzabadi, Cecilia H.; Sabatino, David A.

doi:10.1016/j.bmcl.2013.07.030

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…Similarly, a new class of DNA binding nucleolipid was developed from an efficient N ‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ) coupling strategy. This nucleolipid, 21 , was found to bind to the glucose‐regulated protein of 78 kDa (GRP78) oncogenes, while exhibiting potent and selective antileukemic activity at 10 μ m across a panel of 60 tumor cell types at the US National Cancer Institute (NCI) . A highly functionalized aminoacyl nucleolipid based on uridine was also reported as a cationic surfactant ( 22 ) .…”

Section: Nucleoside and Nucleotide Bioconjugates In Cancer Therapymentioning

confidence: 99%

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

et al. 2015

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Nucleoside- and nucleotide-based chemotherapeutics have been used to treat cancer for more than 50 years. However, their inherent cytotoxicities and the emergent resistance of tumors against treatment has inspired a new wave of compounds in which the overall pharmacological profile of the bioactive nucleic acid component is improved by conjugation with delivery vectors, small-molecule drugs, and/or imaging modalities. In this manner, nucleic acid bioconjugates have the potential for targeting and effecting multiple biological processes in tumors, leading to synergistic antitumor effects. Consequently, tumor resistance and recurrence is mitigated, leading to more effective forms of cancer therapy. Bioorthogonal chemistry has led to the development of new nucleoside bioconjugates, which have served to improve treatment efficacy en route towards FDA approval. Similarly, oligonucleotide bioconjugates have shown encouraging preclinical and clinical results. The modified oligonucleotides and their pharmaceutically active formulations have addressed many weaknesses of oligonucleotide-based drugs. They have also paved the way for important advancements in cancer diagnosis and treatment. Cancer-targeting ligands such as small-molecules, peptides, and monoclonal antibody fragments have all been successfully applied in oligonucleotide bioconjugation and have shown promising anticancer effects in vitro and in vivo. Thus, the application of bioorthogonal chemistry will, in all likelihood, continue to supply a promising pipeline of nucleic acid bioconjugates for applications in cancer detection and therapy.

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Section: Nucleoside and Nucleotide Bioconjugates In Cancer Therapymentioning

confidence: 99%

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

et al. 2015

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“…Well known examples of antiviral modified guanosines are acyclovir [7], ganciclovir [8] and entecavir [9], which are currently adopted in clinic against HSV, CMV and HBV, respectively. In more recent years, the interest for nucleoside analogues has been rekindled also in the frame of a general revisitation of their potential as anticancer and antibacterial agents [10][11][12][13][14]. We recently described some amphiphilic guanosine analogues as model compounds of a still very poorly investigated class of guanosine derivatives [15].…”

Section: Introductionmentioning

confidence: 99%

Guanine-based amphiphiles: synthesis, ion transport properties and biological activity

Musumeci¹,

Irace

Santamaria

et al. 2015

Bioorganic & Medicinal Chemistry

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“…The GRP78 receptor is a 78 kDa member of the heat shock family of proteins which functions as an intracellular chaperone by regulating protein folding events in the endoplasmic reticulum [15][16][17]. In cancer, GRP78 is overexpressed and cell surface localized, where it exhibits a variety of signaling pathways that induce cancer initiation, proliferation, and metastatic spread [18][19][20][21]. Moreover, GRP78 has been found on the plasma membrane of a variety of cancer cell types but not in normal tissues, making it a valuable biomarker for cancer-targeted therapy [14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…In cancer, GRP78 is overexpressed and cell surface localized, where it exhibits a variety of signaling pathways that induce cancer initiation, proliferation, and metastatic spread [18][19][20][21]. Moreover, GRP78 has been found on the plasma membrane of a variety of cancer cell types but not in normal tissues, making it a valuable biomarker for cancer-targeted therapy [14][15][16][17][18][19][20][21]. Toward this goal, Pep42 has been effectively conjugated with Taxol, and the pro-apoptotic D-(KLAKLAK) 2 sequence triggering programmed cell death specifically in human melanoma cancer cell lines and in xenograft mouse models [22].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization, and biological activity of poly(arginine)-derived cancer-targeting peptides in HepG2 liver cancer cells

et al. 2014

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The solid-phase synthesis, structural characterization, and biological evaluation of a small library of cancer-targeting peptides have been determined in HepG2 hepatoblastoma cells. These peptides are based on the highly specific Pep42 motif, which has been shown to target the glucose-regulated protein 78 receptors overexpressed and exclusively localized on the cell surface of tumors. In this study, Pep42 was designed to contain varying lengths (3-12) of poly(arginine) sequences to assess their influence on peptide structure and biology. Peptides were effectively synthesized by 9-fluorenylmethoxycarbonyl-based solid-phase peptide synthesis, in which the use of a poly(ethylene glycol) resin provided good yields (14-46%) and crude purities >95% as analyzed by liquid chromatography-mass spectrometry. Peptide structure and biophysical properties were investigated using circular dichroism spectroscopy. Interestingly, peptides displayed secondary structures that were contingent on solvent and length of the poly(arginine) sequences. Peptides exhibited helical and turn conformations, while retaining significant thermal stability. Structure-activity relationship studies conducted by flow cytometry and confocal microscopy revealed that the poly(arginine) derived Pep42 sequences maintained glucose-regulated protein 78 binding on HepG2 cells while exhibiting cell translocation activity that was contingent on the length of the poly(arginine) strand. In single dose (0.15 mM) and dose-response (0-1.5 mM) cell viability assays, peptides were found to be nontoxic in human HepG2 liver cancer cells, illustrating their potential as safe cancer-targeting delivery agents.

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Synthesis, DNA binding and anti-leukemic activity of an aminoacyl nucleolipid

Cited by 9 publications

References 37 publications

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

Nucleic Acid Bioconjugates in Cancer Detection and Therapy

Guanine-based amphiphiles: synthesis, ion transport properties and biological activity

Synthesis, characterization, and biological activity of poly(arginine)-derived cancer-targeting peptides in HepG2 liver cancer cells

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