Article
Chemistry, Multidisciplinary
Dongyuan Wang, Yuan Tian, Yu Zhang, Xiaona Sun, Yuxuan Wu, Ruping Liu, Fang Zeng, Jingjing Du, Kuan Hu
Summary: This study identified a multifunctional peptide drug conjugate (PDC) as a safe and efficient carrier to deliver AS1411 to the nucleus of cancer cells. The PDC showed unexpected synergy with AS1411, enhancing its anticancer effect and reversing the stemness of cancer stem-like cells.
Review
Oncology
Lamiaa Mohamed Ahmed Ali, Magali Gary-Bobo
Summary: The objective of this review is to focus on different nanovectors that can transport siRNA to block the expression of genes responsible for cancer development. Nanomedicine and phototherapy are becoming more important in the race to design more effective and targeted therapies. This review highlights the design of nanovectors that can transport siRNAs and release them through controlled light excitation to turn off deregulated genes in cancer cells.
Article
Pharmacology & Pharmacy
Kristina Kiisholts, Kaido Kurrikoff, Piret Arukuusk, Ly Porosk, Maire Peters, Andres Salumets, Uelo Langel
Summary: Gene therapy using CPPs as delivery vectors shows potential for treating endometriosis and cancer by inhibiting cellular proliferation and invasion through siRNA nanoparticles. Combining gene therapy with hormonal treatment may provide synergistic effects for endometriosis therapy.
Article
Polymer Science
Yi-Yang Peng, Haimei Hu, Diana Diaz-Dussan, Jianyang Zhao, Xiaojuan Hao, Ravin Narain
Summary: This study developed a novel modification strategy by conjugating cell-penetrating peptides to polymers, resulting in the formation of polymer complexes with multivalent cell-penetrating peptides. These complexes showed enhanced cellular uptake of siRNA and improved silencing efficiency through enhanced endosomal escape.
Article
Chemistry, Multidisciplinary
Venkatesh Ravula, Yu-Lun Lo, Li-Fang Wang, Srilakshmi Patri
Summary: A novel cationic gemini lipopeptide (ATTA) was designed, synthesized, and applied for gene delivery, significantly enhancing transfection efficiency and cell-selective cytotoxicity. The inclusion of an optimal ratio of ATTA in liposomes improved transfection efficiency in various human cell lines, showing distinct activity between cancerous and noncancerous cell lines. Lipoplexes of ATTA-containing formulations with an anticancer therapeutic gene induced more cytotoxicity than conventional formulations, suggesting the potential of arginine-rich cationic lipopeptide in enhancing gene delivery vector formulations.
Article
Chemistry, Organic
Vikram Thimaradka, Hayata Utsunomiya, Tomonori Tamura, Itaru Hamachi
Summary: The His-tag/NiNTA interaction promotes a new catalytic protein acylation strategy, enabling selective protein labeling in biological milieu. The recognition-assisted activation mechanism allows for efficient protein labeling at lower substrate concentrations, enabling highly selective and efficient cell-surface receptor modification in live cells.
Article
Pharmacology & Pharmacy
Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari
Summary: Recent approvals of siRNA-based products have led to exploration of siRNA as a potential treatment option for cancer and other diseases. This study introduces a series of oleyl-conjugated histidine-arginine peptides as a promising nonviral siRNA delivery tool.
Article
Pharmacology & Pharmacy
Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi
Summary: In this study, several linear peptides containing tryptophan (W) and arginine (R) residues were designed and synthesized. These peptides were attached to lipophilic fatty acyl chains, cholesterol, or PEG. The newly developed peptides efficiently protected siRNA against early degradation and successfully delivered siRNA into cells, resulting in significant downregulation of target proteins.
Article
Oncology
Kuebra Kaban, Clemens Hinterleitner, Yanjun Zhou, Emine Salva, Ayse Gulten Kantarci, Helmut R. Salih, Melanie Maerklin
Summary: The overexpression of antiapoptotic protein BCL-2 is linked with ER expression in breast cancer, and a novel treatment strategy using NK cell-derived exosomes as carriers for BCL-2 targeted siRNAs has been proposed. This approach has shown to enhance the killing ability of NK cell-derived exosomes by silencing BCL-2 overexpression and targeting oncogenes in breast cancer.
Article
Medicine, Research & Experimental
Parisa Lotfinejad, Tohid Kazemi, Sahar Safaei, Mohammad Amini, Elmira Roshani Asl, Elham Baghbani, Siamak Sandoghchian Shotorbani, Farhad Jadidi Niaragh, Afshin Derakhshani, Mahdi Abdoli Shadbad, Nicola Silvestris, Behzad Baradaran
Summary: TNBC with high PD-L1 expression can induce an immunosuppressive tumor microenvironment, but targeting PD-L1 through siRNA can reduce its expression, decrease cancer cell proliferation, induce apoptosis, and effectively inhibit cell migration.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Melissa Siaw Han Lim, Yuki Nishiyama, Takashi Ohtsuki, Kazunori Watanabe, Hirotsugu Kobuchi, Kazuko Kobayashi, Eiji Matsuura
Summary: A novel A(3)B type Lactosome conjugated with cell-penetrating peptide and ATP-binding cassette transporter G2 siRNA was developed for inducing apoptosis in cancer cells. By utilizing the enhanced cellular uptake by a photosensitizer and the photoinduced cytosolic dispersion, efficient delivery of siRNA for gene silencing was achieved.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Andrea Carolina Barragan-Cardenas, Diego Sebastian Insuasty-Cepeda, Yerly Vargas-Casanova, Joel Edmundo Lopez-Meza, Claudia Marcela Parra-Giraldo, Ricardo Fierro-Medina, Zuly Jenny Rivera-Monroy, Javier Eduardo Garcia-Castaneda
Summary: Breast cancer is a leading cause of premature death in women, with current treatments causing significant physical and psychological side effects. The palindromic peptide R-1-R (RWQWRWQWR) shows selective cytotoxicity against cancer cells. Modifications involving the inclusion of arginine in the N-terminal end of the peptide increased its cytotoxicity against breast cancer cell lines and induced apoptotic cell death. This study presents a promising peptide modification for improving anticancer peptides.
Article
Pharmacology & Pharmacy
Adhika Balgobind, Aliscia Daniels, Mario Ariatti, Moganavelli Singh
Summary: This study assessed the efficacy of cationic lipid-based systems for the delivery of HER2/neu siRNA in breast cancer. The results showed that cationic liposomes efficiently bound, compacted, and protected the therapeutic siRNA against degradation. The non-PEGylated Chol-T-siRNA lipoplexes exhibited the highest HER2/neu silencing.
Article
Biochemistry & Molecular Biology
Andrea Peier, Lan Ge, Nicolas Boyer, John Frost, Ruchia Duggal, Kaustav Biswas, Scott Edmondson, Jeffrey D. Hermes, Lin Yan, Chad Zimprich, Ahmad Sadruddin, Hung Yi Kristal Kaan, Arun Chandramohan, Christopher J. Brown, Dawn Thean, Xue Er Lee, Tsz Ying Yuen, Fernando J. Ferrer-Gago, Charles W. Johannes, David P. Lane, Brad Sherborne, Cesear Corona, Matthew B. Robers, Tomi K. Sawyer, Anthony W. Partridge
Summary: Macrocyclic peptides present a new avenue for targeting intracellular PPIs, but achieving sufficient membrane permeability is a central challenge. The NanoClick assay, which measures peptide exposure in cells in a concentration-dependent manner, can serve as a screening tool to optimize structure-activity-permeability relationships for functionally active molecules.
ACS CHEMICAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Shahin Aghamiri, Farshid Zandsalimi, Pourya Raee, Mohammad-Amin Abdollahifar, Shing Cheng Tan, Teck Yew Low, Sajad Najafi, Milad Ashrafizadeh, Ali Zarrabi, Hossein Ghanbarian, Mojgan Bandehpour
Summary: Breast cancer is the most common and deadliest cancer in women worldwide, with notable advances in treatment but still low survival rates for metastatic patients. Antimicrobial peptides (AMPs) have garnered attention for their cost-effectiveness and high specificity, though clinical data on their efficacy is lacking, emphasizing the need for clinical trials.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Physiology
Young-Woo Nam, Meng Cui, Razan Orfali, Adam Viegas, Misa Nguyen, Eman H. M. Mohammed, Khalid A. Zoghebi, Simin Rahighi, Keykavous Parang, Miao Zhang
Summary: The hydrophobic interactions between the HA helix and the S4-S5 linker are found to be the main determinant of channel apparent Ca(2+) sensitivity in SK2 channels. Mutations that alter the hydrophobicity at this interface can lead to either hypersensitivity or hyposensitivity to Ca2+. This study highlights the crucial role of interactions between the HA helix and S4-S5 linker in regulating the Ca(2+) sensitivity of SK2 channels.
Article
Medicine, Research & Experimental
Ryley Hall, Abdulaziz Alasmari, Saghar Mozaffari, Parvin Mandipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi
Summary: Researchers developed a multicomponent delivery system called peptide lipid-associated nucleic acids (PLANAs) to encapsulate siRNA efficiently and achieve protein silencing in cancer cells.
MOLECULAR PHARMACEUTICS
(2021)
Review
Biochemistry & Molecular Biology
Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha AlKhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth
Summary: Peptides, as fragments of proteins, play vital roles in biological processes with unique characteristics and promising potentials in biotherapies. Current research focuses on short peptide-based therapeutic developments, covering disease treatments, biosynthesis, nanotechnology, peptide limitations overcoming, among others.
Article
Multidisciplinary Sciences
Shinichi Fukuda, Akhil Varshney, Benjamin J. Fowler, Shao-bin Wang, Siddharth Narendran, Kameshwari Ambati, Tetsuhiro Yasuma, Joseph Magagnoli, Hannah Leung, Shuichiro Hirahara, Yosuke Nagasaka, Reo Yasuma, Ivana Apicella, Felipe Pereira, Ryan D. Makin, Eamonn Magner, Xinan Liu, Jian Sun, Mo Wang, Kirstie Baker, Kenneth M. Marion, Xiwen Huang, Elmira Baghdasaryan, Meenakshi Ambati, Vidya L. Ambati, Akshat Pandey, Lekha Pandya, Tammy Cummings, Daipayan Banerjee, Peirong Huang, Praveen Yerramothu, Genrich Tolstonog, Ulrike Held, Jennifer A. Erwin, Apua C. M. Paquola, Joseph R. Herdy, Yuichiro Ogura, Hiroko Terasaki, Tetsuro Oshika, Shaban Darwish, Ramendra K. Singh, Saghar Mozaffari, Deepak Bhattarai, Kyung Bo Kim, James W. Hardin, Charles L. Bennett, David R. Hinton, Timothy E. Hanson, Christian Rover, Keykavous Parang, Nagaraj Kerur, Jinze Liu, Brian C. Werner, S. Scott Sutton, Srinivas R. Sadda, Gerald G. Schumann, Bradley D. Gelfand, Fred H. Gage, Jayakrishna Ambati
Summary: Alu retrotransposons propagate through reverse transcription using L1 elements, with cytoplasmic Alu cDNA inducing retinal pigmented epithelium degeneration independently of integration. Inhibitors of this process may be potential therapies for atrophic macular degeneration.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Medicinal
Michel F. Sanner, Khalid Zoghebi, Samara Hanna, Saghar Mozaffari, Simin Rahighi, Rakesh K. Tiwari, Keykavous Parang
Summary: The cyclic peptide [WR](9) has been identified as a potent tyrosine kinase inhibitor, exhibiting higher inhibitory activity than other peptides against a variety of selected protein kinases. Molecular dynamics simulations suggest that [WR](9) affects the plasticity of the protein and the volume of the ATP binding site pocket, potentially contributing to its increased affinity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Medicinal
Naglaa Salem El-Sayed, Alexander S. Jureka, Megan R. Edwards, Sandeep Lohan, Caroline G. Williams, Patrick T. Keiser, Robert A. Davey, Jennifer Totonchy, Rakesh K. Tiwari, Christopher F. Basler, Keykavous Parang
Summary: This study describes the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their antiviral activity. Mono-fatty acyl conjugates showed weaker activity compared to RDV, but fatty acylation could improve the half-life and antiviral activity of RDV.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Razan Alhazmi, Shirley Tong, Shaban Darwish, Elina Khanjani, Bharti Khungar, Swati Chawla, Zhonghui Zheng, Richard Chamberlin, Keykavous Parang, Sun Yang
Summary: A novel APE/Ref-1 inhibitor was synthesized and found to significantly inhibit tumor growth in a mouse model of melanoma. No significant systemic toxicity was observed. Compound 11, an analog of the inhibitor, exhibited potent anti-melanoma activities and improved water solubility compared to its parental compound 2. Targeting APE/Ref-1-mediated signaling using pharmaceutical inhibitors is a novel and effective strategy for melanoma treatment with potentially high impact.
Article
Biochemistry & Molecular Biology
Aaminat Qureshi, Louise A. Ouattara, Naglaa Salem El-Sayed, Amita Verma, Gustavo F. Doncel, Muhammad Iqbal Choudhary, Hina Siddiqui, Keykavous Parang
Summary: In this study, the conjugation or combination of the lipophilic amide bond with nucleotide-based tenofovir (TFV) was hypothesized to improve the anti-HIV activity. Several derivatives were synthesized and evaluated for their anti-HIV activity. Results showed that some of the synthesized compounds exhibited stronger inhibitory effects than the parent drug TFV, and certain compounds were more potent than tenofovir alafenamide (TAF) at the molar concentration.
Article
Biochemistry & Molecular Biology
Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari
Summary: The hybrid compounds of benzopyran-4-ones and isoxazoles were designed and synthesized, and they exhibited significant antiproliferative activity against multiple cancer cell lines and anti-inflammatory activity. Compound 5a showed selective anticancer activity and the ability to induce apoptosis in cancer cells.
Article
Pharmacology & Pharmacy
Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi
Summary: In this study, several linear peptides containing tryptophan (W) and arginine (R) residues were designed and synthesized. These peptides were attached to lipophilic fatty acyl chains, cholesterol, or PEG. The newly developed peptides efficiently protected siRNA against early degradation and successfully delivered siRNA into cells, resulting in significant downregulation of target proteins.
Review
Chemistry, Medicinal
Naiera M. Helmy, Keykavous Parang
Summary: Fungal infections pose a significant threat to human health, and there is a growing interest in antifungal research due to microbial resistance, improper use of antimicrobial drugs, and the need for less toxic treatments. Cyclic peptides, specifically antifungal peptides, have been studied as potential agents since 1948. Recent years have seen increased attention to exploring cyclic peptides as a promising strategy in combating antifungal infections caused by pathogenic fungi. This review highlights antifungal cyclic peptides isolated from various sources, emphasizing the need for further exploration of their therapeutic applications.
Article
Chemistry, Medicinal
Jonathan Moreno, Khalid Zoghebi, David Salehi, Lois Kim, Sorour Khayyatnejad Shoushtari, Rakesh K. Tiwari, Keykavous Parang
Summary: In this study, seven cell-penetrating peptides designed in our laboratory were evaluated for protein delivery. [WR](9) and [DipR](5) were found to be the most efficient peptides and were selected for further studies. Through confocal microscopy and FACS analysis, it was determined that [WR](9) and [DipR](5) were able to successfully deliver proteins.
Article
Biochemistry & Molecular Biology
Jaunetta Hill, Karim E. Shalaby, Syed W. Bihaqi, Bothaina H. Alansi, Benjamin Barlock, Keykavous Parang, Richard Thompson, Khalid Ouararhni, Nasser H. Zawia
Summary: Recent breakthroughs in the field of Alzheimer's disease have led to the development of disease-modifying biologics and diagnostic markers. In this study, tolfenamic acid (TA) was used as a scaffold to develop safer and more potent brain-penetrating analogs that can interfere with DNA binding and modulate the expression of SP1 target genes, reducing the production of AD biomarkers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
