Journal: Nature reviews. Drug discovery

Article Title: Aptamers as targeted therapeutics: current potential and challenges

doi: 10.1038/nrd.2016.199

Figure Lengend Snippet: Comparison of nucleic acid aptamers and protein antibodies

Article Snippet: TriLink , 1996/San Diego, California, USA , R & D support: Solid-phase chemical synthesis of RNA and DNA , Aptamer synthesis, modification and conjugation Random libraries and primers.

Techniques: Comparison, Polymer, Binding Assay, Activity Assay, In Vitro, Selection, High Throughput Screening Assay, In Vivo, Transgenic Assay, Modification, Conjugation Assay, Immunopeptidomics, Filtration, Diagnostic Assay

Journal: Nature reviews. Drug discovery

Article Title: Aptamers as targeted therapeutics: current potential and challenges

doi: 10.1038/nrd.2016.199

Figure Lengend Snippet: Key companies in the global aptamers market

Article Snippet: TriLink , 1996/San Diego, California, USA , R & D support: Solid-phase chemical synthesis of RNA and DNA , Aptamer synthesis, modification and conjugation Random libraries and primers.

Techniques: Modification, Biomarker Discovery, Affinity Purification, Flow Cytometry, Software, Selection, Next-Generation Sequencing, Binding Assay, High Throughput Screening Assay, Isolation, Microscopy, Purification, Animal Model, Diagnostic Assay, Functional Assay, Conjugation Assay

Journal: Nature reviews. Drug discovery

Article Title: Aptamers as targeted therapeutics: current potential and challenges

doi: 10.1038/nrd.2016.199

Figure Lengend Snippet: A) The bivalent 4-1BB aptamer. The 3′-terminus of two 4-1BB aptamers are attached to a 21-nt complementary linker sequence and subsequently annealed together. B) The bivalent OX40 aptamer. The 3′-end linker sequences (20 nt in length) of OX40 aptamers were annealed to a flexible DNA scaffold. A tandem repeat of 20 nt DNA oligos was connected by a flexible polyethylene spacer.

Article Snippet: TriLink , 1996/San Diego, California, USA , R & D support: Solid-phase chemical synthesis of RNA and DNA , Aptamer synthesis, modification and conjugation Random libraries and primers.

Techniques: Sequencing

Journal: Acta Pharmaceutica Sinica. B

Article Title: P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate

doi: 10.1016/j.apsb.2023.03.021

Figure Lengend Snippet: Examples of the involvement of P450 enzymes in nonribosomal peptide biosynthesis. (A) Introduction of a dehydrotyrosine (Dht) residue in WS9326A by P450 Sas (Sas16, red sphere; Dht residue shown in red). (B) Introduction of β -OH groups into residues of skyllamycin by P450 P450 sky (Sky32, blue sphere), with this P450 targeting PCP-bound amino acid substrates during NRPS-mediated peptide assembly through specific interactions with the PCP domain (modified residues shown in blue; other examples of such P450s are have been characterised in the biosynthesis of novobiocin and nikkomycin). R = alkyl side chain. (C) Examples of P450s interacting with the NRPS machinery of the balhimycin GPA: this includes β -hydroxylation of PCP-bound Tyr residues by P450 OxyD (upper, orange sphere labelled D; residues shown in orange) and the side chain crosslinking of NRPS-bound heptapeptide intermediates by P450s OxyA–C (lower panel, red spheres labelled A‒C, location of crosslinks installed shown as red arrows). The former process is governed by P450/PCP interactions, whilst the latter is mediated by P450 interactions with the X-domain that is specific to GPA biosynthesis (shown as a pink sphere labelled X). R, R 1 = sugar moiety. Domain key: PCP–peptidyl carrier protein (yellow sphere; PPant shown as black curved line); A–adenylation domain (grey sphere).

Article Snippet: Solutions of tyrosine, cyclic WS9326B, and linear acylated-peptide analogues of WS9326A (chemically synthesized by solid phase peptide synthesis, GL Biochem (Shanghai) Ltd.) were prepared at a concentration of 1 mmol/L in binding buffer (20 mmol/L Tris-HCl and 500 mmol/L NaCl).

Techniques: Residue, Modification

Journal: Acta Pharmaceutica Sinica. B

Article Title: P450-mediated dehydrotyrosine formation during WS9326 biosynthesis proceeds via dehydrogenation of a specific acylated dipeptide substrate

doi: 10.1016/j.apsb.2023.03.021

Figure Lengend Snippet: The biosynthesis of WS9326A and application of in vivo offloading probes to understand the timing of Dht formation. (A) Overview of the proposed nonribosomal biosynthesis pathway producing WS9326A together with offloaded biosynthetic intermediates 4–16 obtained via the use of chemical probes 1–3 (for structures 4–16 refer to Supporting Information). (B) Structures of chemical probes 1–3 . (C) Examples of putative structures obtained by offloading experiments: 4 and 5 –offloaded from module 1 by 1 (Tyr probe) with concomitant N -methylation of 1 (SI); 8 and 12 –offloaded from modules 2 and 3 by 2 (Gly probe, supporting Information) and 3 ( β -Ala probe, supporting Information) respectively. (D) HR-MS 2 characterisation of the putative offloaded intermediate species 12 , showing both probe- and peptide-related fragments. Colours of the chemical structures denote synthetic probe origin (black), biosynthesis (blue), Dht intermediate (red) and desaturated Tyr probe 1 (magenta). Domain key: PCP–peptidyl carrier protein (yellow sphere; PPant shown as black curved line); A–adenylation domain (green sphere); C–condensation domain (orange sphere); E–epimerisation domain (blue sphere); Mt– N -methyl transferase domain (red sphere); TE–thioesterase domain (purple sphere).

Article Snippet: Solutions of tyrosine, cyclic WS9326B, and linear acylated-peptide analogues of WS9326A (chemically synthesized by solid phase peptide synthesis, GL Biochem (Shanghai) Ltd.) were prepared at a concentration of 1 mmol/L in binding buffer (20 mmol/L Tris-HCl and 500 mmol/L NaCl).

Techniques: In Vivo, Methylation