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Peptide drug conjugate

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https://www.readbyqxmd.com/read/30547028/perfluorophenyl-derivatives-as-unsymmetrical-linkers-for-solid-phase-conjugation
#1
Saba Alapour, Anamika Sharma, Beatriz G de la Torre, Deresh Ramjugernath, Neil A Koorbanally, Fernando Albericio
Linkers play major roles in conjugation chemistry toward the advancement of drug discovery. Two different series of fluorinated linkers were introduced to the backbone of a model peptide using solid phase peptide synthesis. These fluorinated linkers have the potential to conjugate two asymmetrical groups. This has not been done using other fluorinated linkers. This study deals with application of linkers with S, N, and O terminals and reports on the investigation of their chemoselectivity and activity for branching peptide backbones using a chosen model peptide...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/30539365/peptide-nanoparticle-conjugates-a-next-generation-of-diagnostic-and-therapeutic-platforms
#2
REVIEW
Woo-Jin Jeong, Jiyoon Bu, Luke J Kubiatowicz, Stephanie S Chen, YoungSoo Kim, Seungpyo Hong
Peptide-nanoparticle conjugates (PNCs) have recently emerged as a versatile tool for biomedical applications. Synergism between the two promising classes of materials allows enhanced control over their biological behaviors, overcoming intrinsic limitations of the individual materials. Over the past decades, a myriad of PNCs has been developed for various applications, such as drug delivery, inhibition of pathogenic biomolecular interactions, molecular imaging, and liquid biopsy. This paper provides a comprehensive overview of existing technologies that have been recently developed in the broad field of PNCs, offering a guideline especially for investigators who are new to this field...
December 12, 2018: Nano Convergence
https://www.readbyqxmd.com/read/30538465/fabrication-and-evaluation-of-a-%C3%AE-pga-based-self-assembly-transferrin-receptor-targeting-anticancer-drug-carrier
#3
Li Zhang, Xiaoyu Zhu, Shijia Wu, Yazhou Chen, Shiming Tan, Yingjie Liu, Wenzheng Jiang, Jing Huang
Background: cis-Dichlorodiamineplatinum (CDDP) was one of the most common used drugs in clinic for cancer treatment. However, CDDP caused a variety of side effects. The abundant carboxyl groups on the surface of poly glutamic acid (PGA) could be modified with various kinds of targeted ligands. PGA delivery system loaded CDDP for cancer therapies possesses potential to overcome the side effects. Materials and methods: In this study, we constructed a safe and efficient anticancer drug delivery system PGA-Asp-maleimide-cisplatin-peptide complex (PAMCP), which was loaded with CDDP and conjugated with the transferrin receptor (TFR)-targeting peptide through a maleimide functional linker...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30537284/treating-tumors-at-low-drug-doses-using-an-aptamer-peptide-synergistic-drug-conjugate
#4
Anusha Pusuluri, Vinu Krishnan, Valerie Lensch, Apoorva Sarode, Elaine Bunyan, Douglas Vogus, Stefano Menegatti, H Tom Soh, Samir Mitragotri
Combination chemotherapy must strike a difficult balance between safety and efficacy. Current regimens suffer from poor therapeutic impact because drugs are given at their maximum tolerated dose (MTD), which compounds the toxicity risk and exposes tumors to non-optimal drug ratios. We developed a modular framework that selectively delivers drug combinations at synergistic ratios via tumor-targeting aptamers for effective low-dose treatment. Specifically, we coupled a nucleolin recognizing aptamer to peptide scaffolds laden with precise ratios of doxorubicin (DOX) and camptothecin (CPT)...
December 11, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/30532537/bufalin-loaded-vitamin-e-succinate-grafted-chitosan-oligosaccharide-rgd-conjugated-tpgs-mixed-micelles-demonstrated-improved-antitumor-activity-against-drug-resistant-colon-cancer
#5
Zeting Yuan, Yuxia Yuan, Lin Han, Yanyan Qiu, Xiaqin Huang, Feng Gao, Guohua Fan, Yixi Zhang, Xueyao Tang, Xue He, Ke Xu, Peihao Yin
Background: Multidrug resistance (MDR) is the major reason for the failure of chemotherapy in colon cancer. Bufalin (BU) is one of the most effective antitumor active constituents in Chansu. Our previous study found that BU can effectively reverse P-glycoprotein (P-gp)-mediated MDR in colon cancer. However, the clinical application of BU is limited due to its low solubility in water and high toxicity. In the present study, a multifunctional delivery system based on vitamin-E- succinate grafted chitosan oligosaccharide (VES-CSO) and cyclic (arginine-glycine-aspartic acid peptide) (RGD)-modified d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared by emulsion solvent evaporation method for targeted delivery of BU to improve the efficacy of drug-resistant colon cancer therapy...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30532536/a666-conjugated-nanoparticles-target-prestin-of-outer-hair-cells-preventing-cisplatin-induced-hearing-loss
#6
Xueling Wang, Yuming Chen, Yong Tao, Yunge Gao, Dehong Yu, Hao Wu
Background: The delivery of treatment agents to inner ear with drug delivery system (DDS) has been under investigation to overcome the limitations of the conventional therapeutic agents in curing or alleviating the cisplatin ototoxicity. Methods: In the present study, a novel targeted dexamethasone (DEX)-loaded DDS, A666-DEX-NP, was constructed for prevention from cisplatin-induced hearing loss. A666-(CLEPRWGFGWWLH) peptides specifically bind to prestin, which is limited to the outer hair cells (OHCs)...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/30529724/a-multifunctional-drug-nanocarrier-for-efficient-anticancer-therapy
#7
Carmen Teijeiro-Valiño, Ramon Novoa-Carballal, Erea Borrajo, Anxo Vidal, Marta Alonso-Nocelo, María de la Fuente Freire, Pedro P Lopez-Casas, Manuel Hidalgo, Noémi Csaba, María José Alonso
So far, the success of anticancer nanomedicines has been moderate due to their lack of adequate targeting properties and/or to their difficulties penetrating tumors. Here we report a multifunctional drug nanocarrier consisting of hyaluronic acid nanocapsules conjugated with the tumor homing peptide tLyp1, which exhibits both, dual targeting properties (to the tumor and to the lymphatics), and enhanced tumor penetration. Data from a 3D co-culture in vitro model showed the capacity of these nanocapsules to interact with the NRP1 receptors over-expressed in cancer cells...
December 7, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30525475/a-peptide-guided-system-with-programmable-subcellular-translocation-for-targeted-therapy-and-bypassing-multidrug-resistance
#8
Yuanyuan Zhu, Yanyan Huang, Yulong Jin, Shilang Gui, Rui Zhao
Non-selectivity and drug resistance are two major obstacles for cancer treatment. Although great advances have been made towards cell targeting or discovering novel delivery pathways, it is still desirable to simultaneously overcome the two hurdles to the success of cancer theranostics. Herein, a peptide-guided system was tailored by modular integration of a cancer biomarker-specific peptide, a mitochondria-targeting motif and a cell toxin. Cell imaging analysis revealed that the dual-targeting peptide-drug conjugate (PDC) features in cancer cell-specific uptake, strong drug retention and programmable intracellular translocation...
December 10, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/30525379/microfluidic-nanoassembly-of-bioengineered-chitosan-modified-fcrn-targeted-porous-silicon-nanoparticles-hypromellose-acetate-succinate-for-oral-delivery-of-anti-diabetic-peptides
#9
João Martins, Dongfei Liu, Flavia Fontana, Mónica Ferreira, Alexandra Correia, Silvia Valentino, Marianna Kemell, Karina Moslova, Ermei M Mäkilä, Jarno J Salonen, Jouni Hirvonen, Bruno Sarmento, Hélder A Santos
Microfluidics technology is emerging as a promising strategy to improve the oral delivery of proteins and peptides. Herein, a multistage drug delivery system is proposed as a step forward in the development of non-invasive therapies. Undecylenic acid modified thermally hydrocarbonized porous silicon (UnPSi) nanoparticles (NPs) were functionalized with the Fc fragment of immunoglobulin G for targeting purposes. Glucagon like peptide-1 (GLP-1) was loaded into the NPs as a model anti-diabetic drug. Fc-UnPSi NPs were coated with mucoadhesive chitosan, and ultimately entrapped into a polymeric matrix with pH-responsive properties by microfluidic nanoprecipitation...
December 7, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30523991/development-of-a-novel-drug-targeting-delivery-system-for-cervical-cancer-therapy
#10
Li Xiao, Ni Ma, Huimin He, Jinmei Li, Sinan Cheng, Qian Yang, Yifan Hou, Fengying Song, Huijuan Jin, Xiaorong Su, Jing Dong, Ruiye Zuo, Xigui Song, Wei Duan, Yingchun Hou
"Targeting peptides" have demonstrated their value in diagnostic imaging and therapy and novel peptide probes specific to cervical cancer were developed. In the M13KE phage dodecapeptide (12-mer) peptide library, the phage clone S7 showed the best binding to the cancer cells as confirmed by immunofluorescence and flow cytometry assays, was selected for continued studies. Its binding peptide, CSP3, was synthesized from the sequence of S7's 12-mer at the N-terminus of the minor coat protein pIII of this M13KE phage vector...
November 26, 2018: Nanotechnology
https://www.readbyqxmd.com/read/30521347/antibody-assisted-delivery-of-a-peptide-drug-conjugate-for-targeted-cancer-therapy
#11
Hyungjun Kim, Do Been Hwang, Minsuk Choi, Soyoung Lee, Sukmo Kang, Yonghyun Lee, Sunghyun Kim, Junho Chung, Sangyong Jon
A number of cancer-targeting peptide-drug conjugates (PDCs) have been explored as alternatives to antibody-drug conjugates (ADCs) for targeted cancer therapy. However, the much shorter circulation half-life of PDCs compared with ADCs in vivo has limited their therapeutic value and thus their translation into the clinic, highlighting the need to develop new approaches for extending the half-life of PDCs. Here, we report a new strategy for targeted cancer therapy of a PDC based on a molecular hybrid between an anti-hapten antibody and a hapten-labeled PDC...
December 6, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/30511654/cancer-targeted-and-glutathione-responsive-micellar-carriers-for-controlled-delivery-of-cabazitaxel
#12
Xiaoxiong Han, Feirong Gong, Lili Chi, Caochuan Feng, Jing Sun, Yiyang Chen, Jianwen Liu, Yaling Shen
Novel type of multifunctional polymeric micelles (PMs) designated as HM-PMss/CTX micelles were developed in the present study for tumor-targeted and glutathione (GSH)-responsive delivery of cabazitaxel (CTX). The surface of the vehicles was modified with piloting molecules (HM-3 peptide), which targets α v β 3 integrin overexpressed on cancer cells, and the micelle core was cross-linked by GSH-disintegrable disulfide linkages for controlled drug release. HM-PMss/CTX micelles were prepared using a mixture of two functionalized amphiphilic block copolymers and found to physically encapsulate CTX with excellent entrapment efficiency (93...
December 4, 2018: Nanotechnology
https://www.readbyqxmd.com/read/30508486/acid-induced-activated-cell-penetrating-peptide-modified-cholesterol-conjugated-polyoxyethylene-sorbitol-oleate-mixed-micelles-for-ph-triggered-drug-release-and-efficient-brain-tumor-targeting-based-on-a-charge-reversal-mechanism
#13
Yu Tian, Gujie Mi, Qian Chen, Birendra Chaurasiya, Yanan Li, Di Shi, Yong Zhang, Thomas J Webster, Chunmeng Sun, Yan Shen
Glioblastoma multiforme is the most devastating malignant brain tumor in adults. Even with standard-care of therapy, the prognosis remains dismal due to tumor heterogeneity, tumor infiltration, and more importantly, the restrictive nature of the blood-brain barrier (BBB). To overcome the challenge of effectively delivering therapeutic cargo into the brain, herein a "smart," multifunctional polymeric micelle was developed using a cholesterol-conjugated polyoxyethylene sorbitol oleate. A cell penetrating peptide, arginine-glycine repeats (RG)5, was incorporated into the micelles to improve cellular uptake while a pH-sensitive masking sequence, histidine-glutamic acid repeats (HE)5, was introduced for charge shielding to minimize non-specific binding and uptake at physiological pH values...
December 3, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/30505656/mitochondria-targeting-drug-conjugates-for-cytotoxic-anti-oxidizing-and-sensing-purposes-current-strategies-and-future-perspectives
#14
REVIEW
Gantumur Battogtokh, Yeon Su Choi, Dong Seop Kang, Sang Jun Park, Min Suk Shim, Kang Moo Huh, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee, Han Chang Kang
Mitochondrial targeting is a promising approach for solving current issues in clinical application of chemotherapy and diagnosis of several disorders. Here, we discuss direct conjugation of mitochondrial-targeting moieties to anticancer drugs, antioxidants and sensor molecules. Among them, the most widely applied mitochondrial targeting moiety is triphenylphosphonium (TPP), which is a delocalized cationic lipid that readily accumulates and penetrates through the mitochondrial membrane due to the highly negative mitochondrial membrane potential...
October 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/30501963/bh3-mimetics-derived-from-bim-bh3-domain-core-region-show-ptp1b-inhibitory-activity
#15
Xiao Lu, Lijuan Wu, Xiaochun Liu, Shulin Wang, Chuanliang Zhang
A series of our previously described BH3 peptide mimetics derived from Bim-BH3 domain core region were found to exhibit weak to potent PTP1B binding affinity and inhibitory activities via target-based drug screening. Among these compounds, a 12-aa Bim-BH3 core sequence peptide conjugated to palmitic acid (SM-6) displayed good PTP1B binding affinity (KD  = 8.38 nmol/L), inhibitory activity (IC50  = 1.20 μmol/L) and selectivity against other PTPs (TCPTP, LAR, SHP-1 and SHP-2). Furthermore, SM-6 promoted HepG2 cell glucose uptake and inhibited the expression of PTP1B, indicating that SM-6 could improve the insulin resistance effect in the insulin-resistant HepG2 cell model...
November 23, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/30499392/antibiotics-peptide-conjugates-against-multidrug-resistant-bacterial-pathogens
#16
Akinwale Ajayi David, Shang Eun Park, Keykavous Parang, Rakesh Kumar Tiwari
The menace of multi-drug resistance by bacterial pathogens that are responsible for infectious diseases in humans and animals cannot be over-emphasized. Many bacteria develop resistance to antibiotics by one or more combination of resistance mechanisms namely, efflux pump activation thereby reducing bacteria intracellular antibiotic concentration, synthesizing a protein that protects target site causing poor antibiotic affinity to the binding site, or mutations in DNA and topoisomerase gene coding that alters residues in the binding sites...
November 29, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30499020/protein-pegylation-for-cancer-therapy-bench-to-bedside
#17
REVIEW
Vijayalaxmi Gupta, Sneha Bhavanasi, Mohiuddin Quadir, Kevin Singh, Gaurav Ghosh, Kritin Vasamreddy, Arnab Ghosh, Teruna J Siahaan, Snigdha Banerjee, Sushanta K Banerjee
PEGylation is a biochemical modification process of bioactive molecules with polyethylene glycol (PEG), which lends several desirable properties to proteins/peptides, antibodies, and vesicles considered to be used for therapy or genetic modification of cells. However, PEGylation of proteins is a complex process and can be carried out using more than one strategy that depends on the nature of the protein and the desired application. Proteins of interest are covalently conjugated or non-covalently complexed with inert PEG strings...
November 29, 2018: Journal of Cell Communication and Signaling
https://www.readbyqxmd.com/read/30489688/an-immuno-pcr-screen-for-the-detection-of-cjc-1295-and-other-growth-hormone-releasing-hormone-analogues-in-equine-plasma
#18
Mark Timms, Katherine Ganio, Grace Forbes, Simon Bailey, Rohan Steel
CJC-1295 is a 30 amino acid peptide-based drug that stimulates the release of growth hormone (GH) from the pituitary gland. It is unique among performance enhancing peptides due to the presence of a reactive maleimidopropionic acid group that covalently links the peptide to free thiols on the surface of plasma proteins. Once conjugated, CJC-1295 remains active in the bloodstream for significantly longer than non-conjugated peptide-based drugs that are rapidly excreted. Conjugation of CJC-1295 to plasma proteins prevents its detection by top-down mass spectrometry based peptide screening protocols as it effectively becomes a macromolecular protein with an undefined molecular weight...
November 29, 2018: Drug Testing and Analysis
https://www.readbyqxmd.com/read/30488562/cellular-internalization-induced-aggregation-of-porous-silicon-nanoparticles-for-ultrasound-imaging-and-protein-mediated-protection-of-stem-cells
#19
Shengcai Qi, Pengfei Zhang, Ming Ma, Minghua Yao, Jinjin Wu, Ermei Mäkilä, Jarno Salonen, Heikki Ruskoaho, Yuanzhi Xu, Hélder A Santos, Hongbo Zhang
Nanotechnology employs multifunctional engineered materials in the nanoscale range that provides many opportunities for translational stem cell research and therapy. Here, a cell-penetrating peptide (virus-1 transactivator of transcription)-conjugated, porous silicon nanoparticle (TPSi NP) loaded with the Wnt3a protein to increase both the cell survival rate and the delivery precision of stem cell transplantation via a combinational theranostic strategy is presented. The TPSi NP with a pore size of 10.7 nm and inorganic framework enables high-efficiency loading of Wnt3a, prolongs Wnt3a release, and increases antioxidative stress activity in the labeled mesenchymal stem cells (MSCs), which are highly beneficial properties for cell protection in stem cell therapy for myocardial infarction...
November 28, 2018: Small
https://www.readbyqxmd.com/read/30485077/polymer-cancerostatics-targeted-by-recombinant-antibody-fragments-to-gd2-positive-tumor-cells
#20
Robert Pola, Vlastimil Král, Sergey K Filippov, Leonid Kaberov, Tomáš Etrych, Irena Sieglova, Juraj Sedlacek, Milan Fábry, Michal Pechar
A water-soluble polymer cancerostatic actively targeted against cancer cells expressing a disialoganglioside antigen GD2 was designed, synthesized and characterized. A polymer conjugate of an anti-tumor drug doxorubicin with a N-(2-hydroxypropyl)methacrylamide-based copolymer was specifically targeted against GD2 antigen-positive tumor cells using a recombinant single chain fragment (scFv) of an anti-GD2 monoclonal antibody. The targeting protein ligand was attached to the polymer-drug conjugate either via a covalent bond between the amino groups of the protein using a traditional non-specific aminolytic reaction with a reactive polymer precursor or via a non-covalent but highly specific interaction between bungarotoxin covalently linked to the polymer and the recombinant scFv modified with a C-terminal bungarotoxin-binding peptide...
November 28, 2018: Biomacromolecules
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