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Order Tubulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Rangel et al. (2012, 2013) introduced combinatorial platform technology based on so-called internalizing-phage (iPhage) libraries to identify clones that enter mammalian cells through a receptor-independent mechanism and target-specific organelles as a tool to select ligand peptides and identify their intracellular receptors. To do this, penetratin (pen), an antennapedia-derived peptide, was displayed on the phage envelope and mediated receptor-independent uptake of internalizing phage into cells. It was shown that an iPhage construct displaying an established mitochondria-specific localization signal targeted mitochondria, and that an iPhage random peptide library selected for peptide motifs that localized to different intracellular compartments. As a proof of concept, it was demonstrated that one such peptide, if chemically fused to pen, was internalized receptor-independently, localized to mitochondria, and promoted cell death (Rangel et al. 2012). The detailed protocols of the design, cloning, construction, and production of iPhage-based vectors and libraries, along with basic ligand-receptor identification and validation methodologies for organelle receptors, was published by Rangel et al. (2013).
Drug Development with Radiopharmaceuticals
Published in Martin G. Pomper, Juri G. Gelovani, Benjamin Tsui, Kathleen Gabrielson, Richard Wahl, S. Sam Gambhir, Jeff Bulte, Raymond Gibson, William C. Eckelman, Molecular Imaging in Oncology, 2008
Genomics and proteomics continue to provide a wealth of new drugable targets. This coupled with combinatorial chemistry for small molecule and peptide library synthesis, phage display techniques for targeted peptide and single chain antibody fragment library production, and improved techniques for preparation of immunogenic monoclonal antibodies as well as molecular modeling and high-throughput screening has greatly expanded the chemical space that is searchable for new chemical entities. Evaluating the interaction of the new drugs with the drugable targets is the daunting and challenging task undertaken largely by the pharmaceutical industry to produce a pipeline of new drugs. The successful emergence of effective therapeutics from this pipeline is slowed by the ability to critically evaluate the interaction of the drug with the target and fully assess their toxicity and safety profiles.
Reversing the Formation of Alzheimer Amyloid Fibrils and Blocking Toxic Ca2+ Influx
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
V.M. Ingram, B.J. Blanchard, A. Chen, K. Stafford, B. Stockwell
Using cultured neuronal cells, we have developed two series of useful compounds: (i) ten short so-called Decoy Peptides of D-amino acids, selected from a large peptide library, that block the Abeta-induced calcium-influx; (ii) the selection in a High Throughput Screen of several small molecules that block and reverse Abeta fibril formation and also eliminate the Abeta-induced calcium-influx. We illustrate the effectiveness of decoy peptides and of the first HTS compound in eliminating calcium-influx. Because this HTS compound also effectively reverses Abeta fibrils, it is a good candidate for Alzheimer therapy, as are the Decoy Peptides.
An optimized agonist peptide of protease-activated receptor 4 and its use in a validated platelet-aggregation assay
Published in Platelets, 2022
Jing Yang, Claudio Mapelli, Zhaoqing Wang, Chi Shing Sum, Ji Hua, R. Michael Lawrence, Yan Ni, Dietmar A. Seiffert
A phage-display approach was used to identify novel PAR4 APs. For this purpose, a biased peptide library consisting of AYPGXXXXXX, where X is a random natural amino acid, was constructed. The short peptide, AYPG (peptide 16; Table I), was derived from the known PAR4 AP sequence AYPGKF (peptide 1; Table I) [22] and was found to retain modest activity for inducing calcium mobilization in HEK293-PAR4 cells. Six random residues were chosen to maximize library diversity while limiting sequence length to 10 residues. The library quality was verified by DNA sequencing of 78 randomly picked clones, and 20% of the clones had inserts with apparently random distribution of residues in the library segment. The total number of library clones was approximately 109, thus yielding an effective library size of approximately 2 × 108.
Is a non-cytotoxic and non-genotoxic novel bioinspired dipeptide structure synthesis possible for theragnostic applications?
Published in Drug and Chemical Toxicology, 2023
Merve Bacanlı, Jülide Secerli, Burcu Karayavuz, Onur Erdem, Hakan Erdoğan
Peptides, fragments of proteins, are composed of amino acids linked by amide bonds, generally within 50 amino acids in length, and widely found in bioorganisms. Peptides are intrinsically biodegradable and biocompatible. Moreover, this homogeneity also ensures peptides’ bioactivity, including specific site binding, stimulus response, and therapy. These properties make the peptides perfect building blocks for biomedical applications. In recent years, the improvement of synthetic methodology and peptide library screening ensure peptides be vastly utilized as targeting ligand, bioresponsive moiety, and therapeutic agents in biomedical systems including theragnostics (Rong et al.2020).
A novel polymerase β inhibitor from phage displayed peptide library augments the anti-tumour effects of temozolomide on colorectal cancer
Published in Journal of Chemotherapy, 2022
Lihong Qin, Mao Huiwen, Jianguo Wang, Yuanyaun Wang, Salman A. Khan, Ying Zhang, Hong Qiu, Longwei Jiang, Lingfeng He, Yan Zhang, Shaochang Jia
Phage display peptide library has become a crucial platform which offers a rapid, efficient and relatively inexpensive method for the discovery of candidates suitable for drug development. The phage display peptide library Ph.D.-12TM (we used in this article) contains a reservoir size of 6.8 × 1010 clones while a chemical library allows testing of only hundreds or thousands of synthetic compounds [30]. In addition, phage displayed peptides seem to be better molecular agents due to their small size, rapid blood clearance, higher affinity and specificity, greater stability, easier manufacturing, lower cost of large-scale production and better tissue penetration.