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Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Cyclic peptides, also referred as ‘macrocyclic’ compounds, inhibit HDAC by interacting with the outer rim of the enzyme (Mwakwari et al., 2010). These cyclic compounds usually contain complex cap-groups which bind to the HDAC’s outer rim regions, thereby inhibiting the enzyme activity with more potency and isoform selectivity (Maolanon et al., 2016). Based on their macrocyclic moieties, these HDACi are subdivided into: (a) cyclic peptides; and (b) depsipeptides. The first class contains a mixture of L- and D-amino acids and cyclic amino acids such as proline or pipecolic acid (Mwakwari et al., 2010). Examples of cyclic peptides are trapoxin-A and trapoxin-B, apicidin (a fungal metabolite from fusarium species), azumamide (isolated from Mycale izuensis) and HC-toxin (Mwakwari et al., 2010).
Non-FDG radionuclide imaging and targeted therapies
Published in Anju Sahdev, Sarah J. Vinnicombe, Husband & Reznek's Imaging in Oncology, 2020
Luigi Aloj, Ferdia A Gallagher
This receptor system has been implicated in the molecular mechanisms that favour development of metastases. Expression of this receptor in cancer cells favours homing to tissues that express its natural ligand, stromal derived factor 1 (SDF-1), also known as CXCL12. Small peptides targeting CXCR4 were originally developed in the late 1990s (45). Derivatives of the T140 peptide were initially modified for radiolabelling in order to obtain CXCR4-targeting radiopharmaceuticals. Biodistribution properties of these first-generation compounds proved to be unsuitable for successful application. In the early 2000s a small cyclic peptide with more favourable biodistribution properties was identified (46). This compound (GPCR04) has been utilized in preliminary clinical studies in patients with myeloma (47), glioblastoma (48), and lung cancer (49). As CXCR4 is a potential therapeutic target, the main role of these diagnostic agents in the clinic is to establish and quantify receptor expression in tumours. There is also initial clinical experience on targeting CXCR4 expression for radionuclide therapy (50,51).
Role of Plant-Based Bioflavonoids in Combating Tuberculosis
Published in Megh R. Goyal, Durgesh Nandini Chauhan, Assessment of Medicinal Plants for Human Health, 2020
Alka Pawar, Yatendra Kumar Satija
Both kanamycin and amikacin belong to aminoglycosides class of antibiotics. They target mainly the 16S ribosomal subunit and subsequently inhibit the protein biosynthesis. Capreomycin and viomycin are also inhibitors of cyclic peptide. All these four drugs are employed in the therapy of multidrug resistant TB.5
Biotherapeutic effect of cell-penetrating peptides against microbial agents: a review
Published in Tissue Barriers, 2022
Idris Zubairu Sadiq, Aliyu Muhammad, Sanusi Bello Mada, Bashiru Ibrahim, Umar Aliyu Umar
Cyclic cell-penetrating peptides are a relatively new form of peptides with extraordinary therapeutic values and they are usually administered intracellularly to treat difficult conditions such as multidrug-resistant bacterial infections, cancer, and HIV infections.47 For example, L-cyclic peptides were reported to promote cellular absorption of fluorescently labeled phosphopeptide and lamivudine and so also fluorescently labeled conjugate F-[W5R4K] exhibits a highly effective translocation into cells of adenocarcinoma and carcinoma.48 Compared to the linear form of the same peptide, cyclic Tat peptides have been reported to be more successful in cell transduction with bioavailability almost immediately.49 There are about 40 cyclic peptide-based therapeutics on the market, and at least one new cyclic peptide-based medication is introduced per year.50 Cyclic CPPs may aid in targeted drug delivery, for example, a fluorescent protein, mCherry has been targeted to the nucleus and actin cytoskeleton cell compartments after cyclic cell-penetrating peptides induced uptake into living cells, as shown by live cell confocal fluorescence imaging.51 Cyclic CPPs may also improve oral delivery of therapeutic peptides as recent research reported that Oral Coadministration of Zn-Insulin Cyclic Peptide improves its Blood Glucose-Lowering Effect in Mice.52
Strategies for targeting undruggable targets
Published in Expert Opinion on Drug Discovery, 2022
Gong Zhang, Juan Zhang, Yuting Gao, Yangfeng Li, Yizhou Li
Peptide motif participates naturally in PPI. However, the truncated linear peptide does not necessarily fold correctly, losing conformational stability and bioactivity. Therefore, a panel of strategies to stabilize peptide conformation and reduce proteolysis susceptibility have been developed. For α-helix motifs, the staple peptide is an efficient therapeutic entity to facilitate the folding of secondary structures[32]. The cyclic peptide is another classical form of entity, especially for stretched or coiled peptides without well-defined secondary structures[33]. Altogether, the linear/cyclic/staple modes represent diverse peptide conformations adopted to deal with undruggable targets (Figure 1c). Peptidomimetics/proteomimetics represent another category of peptide-derived drugs generated by rational design, display technologies, or library screening. They may contain unnatural amino acid building blocks and cyclic structures, providing advantages over native peptides in aspects of pharmacological property and chemical diversity. Peptidomimetics have been developed to target suppressor of cytokine signaling (SOSC) in the treatment of atherosclerosis and inflammation [34,35].
Small molecule and peptide-based CXCR4 modulators as therapeutic agents. A patent review for the period from 2010 to 2018
Published in Expert Opinion on Therapeutic Patents, 2020
Yesim A Tahirovic, Sameshnee Pelly, Edgars Jecs, Eric J Miller, Savita K Sharma, Dennis C Liotta, Lawrence J Wilson
An application by Mainline Biosciences (US20180066021) covers cyclic peptides of up to 12 amino acids with a cyclic structure comprised of a 7 amino acid sequence with di-sulfur-carbon linkers and up to 5 amino acids (X2-X5) extending from the C-terminal end with capping groups (43) [91]. One position inside the ring (X1) is variable, 4 residues within the cyclic structure are fixed (Tyr, DArg, 2-Nal, Gly) and the bridging residues are sulfur containing residues such as cysteine (m = n = 1) and homo-cysteine (m = n = 2). The di-sulfur bridge consists of a carbon linker with a di-alkyl aryl group (CH2Ar1CH2, a = 1, Ar1 = Ph or naphthyl) chemically bonded to both sulfur atoms or no linker and a sulfur-sulfur bond (a = 0). The application lists 22 claims and has 24 examples with assays including 125I-CXCL12 binding, tumor cell migration and invasion with MDA-MB-231, HCC1806 and A549 cells. The medical and therapeutic uses listed include rheumatoid arthritis, pulmonary fibrosis, HIV infection and cancer (e.g. breast, pancreatic, melanoma, prostate, kidney, neuroblastoma, non-Hodgkin’s lymphoma, lung, ovarian, colorectal, myeloma, glioblastoma and leukemia).