China
Africa
Explore chapters and articles related to this topic
Order Picornavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The 3D structure of poliovirus (PV) type 1 Mahoney, a member of the Enterovirus C species and the causative agent of poliomyelitis, was resolved by x-ray crystallography to 2.9 Å resolution by Hogle et al. (1985). Each of the three major capsid proteins VP1, VP2, and VP3 contained a “core” consisting of an eight-stranded antiparallel β-barrel with two flanking helices. The arrangement of β-strands and helices was structurally similar and topologically identical to the folding pattern of the capsid proteins of the icosahedral plant viruses, as in the case of other picornaviruses. In each of the major capsid proteins, the “connecting loops” and N- and C-terminal extensions were structurally dissimilar. The packing of the subunit “cores” to form the virion shell was reminiscent of the packing in the T = 3 plant viruses but was significantly different in detail. Several of the “connecting loops” and C-terminal strands formed prominent radial projections, which were the antigenic sites of the virion (Hogle et al. (1985). This structure is presented in Figure 27.7.
What Are Polymeric Carriers?
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Gülderen Karakuş, Dolunay Şakar Daşdan
Depending on the peptide sequence, as in the conjugation region proteins, the N-terminus of the sequence may be the C-terminus or a point within it. The conjugation point may be carboxyl (-COOH), amino (-NH2), or sulfhydryl (-SH) ends. Synthetic peptides, haptens, etc., when used as a vaccine, have a significant effect. Nowadays, it is widely used to create specific antibodies. However, therapeutic agents and synthetic peptides or haptens, due to their low solubility, instability, low molecular weight, low antigenic properties, undesirable properties such as biocompatibility, and non-specificity or cytokine toxicity have greatly reduced their ability to act. However, the formation of conjugates of proteins, antigens, or actives with water-soluble polymers significantly changes the properties and immunogenicity of the therapeutic agents.
Radiochemistry for Preclinical Imaging Studies
Published in George C. Kagadis, Nancy L. Ford, Dimitrios N. Karnabatidis, George K. Loudos, Handbook of Small Animal Imaging, 2018
99mTc-maraciclatide (previously known as 99mTc-NC100692) is an eight amino acid peptide based on the RGD motif (Edwards et al. 2008). The RGD unit binds to αvβ3 and αvβ5 integrins, which are biomarkers of angiogenesis. This core unit is flanked by a pair of cysteine residues, which together form an intramolecular disulfide bond. This leads to a cyclic, more rigid peptide exposing the RGD unit, which is favorable for binding to the integrins. A second bridge is formed by another pair of outer amino acids forming a thioether; see Figure 16.4. The chelator is a diamine dioxime with similarities to that in 99mTc-exametazime; see Figure 16.2a. The linker is glutaramide extending the sidechain of the N terminal lysine residue. The C terminus is decorated with a chain of two biomodifiers: a polyethyleneglycol (PEG) oligomer with terminal amino groups followed by diglycolamide. PEGylation generally increases molecular hydrophilicity and the systemic clearance rate in vivo.
A molecular perspective on identifying TRPV1 thermosensitive regions and disentangling polymodal activation
Published in Temperature, 2023
Dustin D. Luu, Aerial M. Owens, Mubark D. Mebrat, Wade D. Van Horn
Beyond the two membrane domains, the majority of the TRPV1 N-terminus comprises six ankyrin repeat domains (ARDs) linked to the S1-S4 domain by a diminutive N-terminal linker region. The C-terminus is composed of a functionally crucial amphipathic TRP helix and a small C-terminal domain. The arrangement of these domains is shown in Figure 2. While it is difficult to overstate the importance of the cryo-EM TRPV1 structures in molecular studies, we note that currently, all TRPV1 structures arise from the rat ortholog. About half are from the full-length channel and the rest are from an engineered rat construct that is missing ~30% of the protein. The engineered construct lacks residues 1–109 from the N-terminus, 765–838 from the C-terminus, and 604–626 from the pore turret loop in the PD. Given the species differences between the rat and human TRPV1 orthologs [1,6], additional structures would benefit the field.
A novel frameshift GP1BB mutation causes autosomal dominant macrothrombocytopenia with decreased vWF receptor expression but normal platelet aggregation
Published in Platelets, 2022
Caitlin Dunstan-Harrison, Ian M. Morison, Elizabeth C. Ledgerwood
The abnormal C-terminal domain could result in misfolding and subsequent proteasomal degradation via the endoplasmic reticulum-associated protein degradation pathway and/or extracellular secretion due to the lack of a transmembrane domain. To investigate whether or not the variant protein could be detected, platelet cell lysates were prepared and analysed by western blotting. WT GP1bβ was present in both the proband and the control (Figure 2A), although when normalised for protein loading only at ~10% of the control compared to the 50% expected (due to being at the sensitivity limit of the antibody used). No band was seen at the predicted molecular weight of the mature mutant protein (~10 kDa larger than WT) consistent with the removal of the majority of the mutant GP1bβ by degradation and/or secretion from the cell. It is possible that the mutant protein is not recognised by the antibody as the 9 of 63 residues in the peptide used to generate the antibody are missing in the mutant protein. However, the use of a polyclonal antibody makes this unlikely, and a probable explanation for the lack of a band is the removal of the mutant GP1bβ.
Endostatin in fibrosis and as a potential candidate of anti-fibrotic therapy
Published in Drug Delivery, 2021
Zequn Zhang, Xi Liu, Zhaolong Shen, Jun Quan, Changwei Lin, Xiaorong Li, Gui Hu
Despite its good anti-fibrotic effects, the use of endostatin has many challenges. First, it is an endogenous molecule and its structural stability needs improvement. Future studies should improve the structure of endostatin to give it stronger anti-fibrotic activity while reducing its antiangiogenic properties and other side effects. Many studies have yielded good results in this regard, including the development of recombinant human endostatin (Endostar) by Chinese researchers. Compared with natural endostatin, Endostar has an added 9 amino acid sequence at the N-terminus, which prolongs its half-life, significantly improving biological activity and stability (Han et al. 2007; Xiao et al. 2015). Moreover, Endostar nano-carriers are reported to maintain it at good concentrations in plasma and tissues (Hu & Zhang 2010; Tong et al. 2010; Chen & Hu 2011). Endostar is now widely used in anticancer therapy. A Japanese study also found that E4, an endostatin-derived peptide, may suppress organ fibrosis. Relative to natural endostatin or recombinant endostatin, E4 has only the C-terminal structure and no N-terminal anti-angiogenic properties, which minimizes side effects. The molecular structure becomes more stable due to C-terminus chemical modification (Yamaguchi et al. 2012; Nishimoto et al. 2015).