China
Africa
Explore chapters and articles related to this topic
Order Patatavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Figure 29.2 shows the genomic structure of the Potyviridae family members. As summarized by Wylie et al. (2017), the genomes range from 8.2–11.3 kb, with an average size of 9.7 kb. The most genomes are monopartite, but those of members of the genus Bymovirus are bipartite. The genomes have a VPg of about 24 kDa, which is covalently linked to the 5′- end, while the 3′-terminus is polyadenylated. The encoded large polyprotein is self-cleaved into a set of functional proteins, and the gene order is generally conserved throughout the family.
Antiviral Activity of Seaweeds and their Extracts
Published in Leonel Pereira, Therapeutic and Nutritional Uses of Algae, 2018
The genome of a virus may consist of DNA or RNA, which may be single stranded (SS) or double stranded (DS), linear or circular. The entire genome may occupy either one nucleic acid molecule (monopartite genome) or several nucleic acid segments (multipartite genome). The different types of genome necessitate different replication strategies (Gelderblom 1991).
Synthesis, in vitro enzyme activity and molecular docking studies of new benzylamine-sulfonamide derivatives as selective MAO-B inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Begüm Nurpelin Sağlık, Derya Osmaniye, Ulviye Acar Çevik, Serkan Levent, Betül Kaya Çavuşoğlu, Özlem Atlı Eklioğlu, Yusuf Özkay, Ali Savaş Koparal, Zafer Asım Kaplancıklı
Currently, the Protein Data Bank contains more than 40 crystal structures of MAO (most of them MAO-B) in complex with different reversible and irreversible inhibitors, as observed through X-ray diffraction at refinements of 3.0–1.7 Å. Additionally, MAO-A shows a markedly different monopartite cavity (∼550 Å) compared to the bipartite cavity (290 Å) found in MAO-B. The “aromatic cage”—a hydrophobic binding pocket containing the FAD cofactor—is considered the active region4,7. The FAD is covalently attached to the cysteine residue of the protein, and the 8α-thioether linkage provides this connection. It is believed that the catalytic activity of the two tyrosine residues, Tyr398 and Tyr435, found in the hMAO-B structure is due to the polarisation of the amine N pair of the substrate12. Therefore, in designing a new inhibitor compound, it is desirable to have the amine group in the structure.
Cell penetrating peptides: the potent multi-cargo intracellular carriers
Published in Expert Opinion on Drug Delivery, 2019
Kimia Kardani, Alireza Milani, Samaneh H. Shabani, Azam Bolhassani
These peptides are short amino acid sequences containing histidine, arginine, and lysine residues, e.g. Tat, poly arginine and poly lysine. The charge of lysine (K) and arginine (R) is positive, but lysine is less effective for cell penetration, alone likely due to the lack of guanidine group. At least eight positive charges are required for effective cellular uptake of cationic CPPs [94]. Although, charged residues are important for cellular penetration, other residues can also be critical. For example, mutation of W14 to F in Penetratin (RQIKIWFQNRRMKWKK) reduced its cellular uptake [95]. A special group of cationic CPPs are nuclear localization sequences (NLSs) harboring lysine-, arginine- or proline-rich motifs which enter the nucleus via the nuclear pore complexes (NPCs). NLSs are classified into monopartite (e.g. SV40: PKKKRKV) and bipartite (e.g. nucleoplasmin: KRPAATKKAGQAKKKL) signals. Other NLSs are TFIIE-β (SKKKKTKV), NF-κB (VQRKRQKLMP), HATF-3 (ERKKRRRE), Oct-6 (GRKRKKRT), and SDC3 (FKKFRKF) [96]. However, NLSs are often covalently linked to a hydrophobic peptide sequence to make an amphipathic CPP with an efficient cell uptake.
Approaches for the discovery of new cell-penetrating peptides
Published in Expert Opinion on Drug Discovery, 2021
Ly Porosk, Ilja Gaidutšik, Ülo Langel
Typically protein sequences are used [5; 6; 10; 24–28]. Proteins have specific motifs, which encode functions generally characterized as binding, posttranslational modifications, and trafficking [25]. Proteins with specific localization, functions, or amino acid patterns may include sequences for prospective CPP sequences, and including these patterns in the peptide sequences may help to fine-tune the interactions between cargo DNA and peptide, or increase specificity by targeting organelles. Proteins, their sequences, and their known functions may give a base upon which new targeting or biologically active peptide (e.g. inhibitor or effector) sequences with cell internalization properties can be derived. For example, a C-terminal H/KDEL sequences provide a signal for retrieval from the Golgi complex [26]. Often, cell-penetrating properties are found in viral protein-derived peptides [27–31] or sequences containing nuclear localization sequences (NLS) [32,33]. NLS is an amino acid motif found in protein sequences that directs protein transport or shuffling between the cytoplasm and the nucleus. The length and features of NLS sequences vary substantially; however, NLS sequences are usually abundant in positively charged residues, with the consensus sequence K-K/R-X-K/R [34]. Monopartite and bipartite NLS motifs have been thoroughly described. They are characterized by a cluster (monopartite) or two clusters (bipartite) of basic residues preceded by a helix-breaking residue or separated by 9–12 residues. There are several variations to this, such as longer linker regions, tri-partide NLS motifs, proline-tyrosine NLS with the motif R/K/H-X(2–5)-P-Y, etc [35]. Overlapping with NLS motifs are molecular sleds, which facilitate the sliding of peptide/protein on DNA [36] and could potentially help to fine tune the interactions between CPPs and nucleic acid.