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Current Inhibitors of Dengue Virus
Published in Venkatesan Jayaprakash, Daniele Castagnolo, Yusuf Özkay, Medicinal Chemistry of Neglected and Tropical Diseases, 2019
J. Jonathan Harburn, G. Stuart Cockerill
A number of molecules have been described as non-peptoid inhibitors of the protease. Typical of a target of this type with a relatively low level of industry interest, inhibitors remain diverse of structure with associated poor structural/development ability properties and moderate levels of potency. Tactics employed in the identification of hits have been to use the known structural information to target the catalytic centre and have invariably used the open form of the protease released in the crystallographic database. Issues that remain with these compounds typically are low permeability and the aforementioned poor drug like properties, e.g., metabolic instability. Perhaps the tractability of this approach can be contextualised by a retrospective view on the closely related Hepatitis C virus (HCV) protease; all protease inhibitors reaching the market in what was a heavily funded series of industry research programmes have been of peptide origin (de Leuw 2018).
Phytonutrients
Published in Parimelazhagan Thangaraj, Medicinal Plants, 2018
Ranganathan Kumar, Sulaxana Kumari Chauhan, Subramanian Vijayalakshmi, Shanmugam Nadanasabapathi
The term ‘alkaloid’ was coined in 1819 by Carl Friedrich Wilhelm Meissner, the German pharmacist, to refer to plant natural products, which was found to show basic properties similar to that of the inorganic alkalis. The ending ‘-oid’ is still in practise even today, which suggests the similarity of their structure or activity, as is evident in modern names such as peptoid, terpenoid or vanilloid (Hesse 2002). Among the secondary metabolites that are produced by plants, the alkaloids act as a very prominent class of defence compounds. Over 21,000 alkaloids have been identified, hence they constitute the largest group among the nitrogen-containing secondary metabolites (besides 700 nonprotein amino acids, 100 amines, 150 alkylamides, 100 glucosinolates and 60 cyanogenic glycosides). Alkaloids are usually present as a mixture of a few major and several minor alkaloids of a particular biosynthetic unit, which differ in functional groups (Wink et al. 2005).
Antimicrobial peptides and other peptide-like therapeutics as promising candidates to combat SARS-CoV-2
Published in Expert Review of Anti-infective Therapy, 2021
Masoumeh Sadat Mousavi Maleki, Mosayeb Rostamian, Hamid Madanchi
Other changes to create peptidomimetics include the binding of β-peptides, peptoids (N-substituted glycines), peptide-peptidomimetic hybrid structures, and lipidization [109]. Peptidomimetics can detect intracellular targets by crossing cell membranes independently (e.g. cyclosporine) or by binding to the cell-penetrating carrier peptides [110]. They can also inhibit protein-protein interactions [111]. Since short peptides are often flexible and unstructured, they can increase their inhibitory potency by stabilizing or inducing the desired secondary structures. Interference of peptidomimetics with protein–protein interactions can occur in all three major structural motifs of the protein: α- helix, β-sheet, and turns. Peptides that mimic these motifs are stabilized in a variety of ways [110].
Prospects for antimicrobial peptide-based immunotherapy approaches in Leishmania control
Published in Expert Review of Anti-infective Therapy, 2018
Farnaz Zahedifard, Sima Rafati
The second disadvantage of AMP is that they are sensitive to some proteases in the body. Some of them can be easily degraded by enzymes, thereby making their half-life in the body to be limited. In addition, it is not possible to use them systemically. Some efforts have been made to find sensitive sequences and change or omit them without affecting the antimicrobial activities [31]. In addition, it is possible to add a synthetic part in order to protect them from proteolytic lyses. Another solution is synthesizing circular structures, which stabilize AMPs against proteases like Novetaxin AMP [22]. It is also possible to add knot-fold structure, which consists of 6 cysteins that make cyclotides. In addition, the synthesis of chimera structures helps peptide to gain more stability like Cecropin A–Melitin hybrids (CAM) [32]. Natural AMPs consist of L form amino acids. It is possible to change the amino acids to D form and amidate C-terminal to increase peptide stability [33]. Another possibility is that peptide-mimicking peptoids are cheaper and more stable against proteases and contain poly-N-substituted glycines [28].
Methods for detecting toxic α-synuclein species as a biomarker for Parkinson’s disease
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Darren M. O’Hara, Suneil K. Kalia, Lorraine V. Kalia
tα-syn can also be detected in the blood, but as red blood cells (RBC) account for greater than 99% of overall α-syn in blood, much of the focus on detecting alterations in levels has focused on serum levels. The influence of RBC contamination and hemolysis are important considerations for the development of a reliable biomarker from blood. Measurement of tα-syn serum and plasma levels can be carried out using a variety of techniques, including standard immunoassays and ELISA, but results have shown wide variation with different groups reporting increases, decreases or no significant changes in tα-syn [44–46]. The most promising method of detecting tα-syn in sera comes from a recent paper by Gao et al. [47], who used a novel high-throughput surface plasmon resonance imaging (SPRi) method to detect a peptoid capable of detecting α-syn. Peptoids are N-substituted oligoglycines with similar structures to peptides, except that the side chains are appended to the nitrogen atom of the backbone instead of the α carbons [48]. They are easy to synthesize, resistant to proteolysis, and have been widely used as probes for recognition of a variety of molecules [49,50]. SPRi is used for studying biomolecular interactions occurring close to the SPR-active metal surface. Gao et al. [47] constructed a peptoid library and their screen identified α-syn binding peptoid-7 (ASBP-7), which bound to α-syn with high specificity and affinity. They found that ASBP-7 was able to detect α-syn in sera from PD patients utilizing the SPRi technique and that it could significantly distinguish PD sera from control sera through binding to α-syn in the sera (Figure 1). This technique appears to be more sensitive than others. However, SPRi will require further validation, as it relies on the principle that there are elevated levels of tα-syn in sera of PD patients.