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Peptide Structure and Analysis
Published in Marco Chinol, Giovanni Paganelli, Radionuclide Peptide Cancer Therapy, 2016
Carlo Pedone, Giancarlo Morelli, Diego Tesauro, Michele Saviano
Amide bond formation involves activation of the carboxyl group of the amino acid. There are four major coupling techniques: (1) in situ coupling reagents such as carbodiimide-mediated coupling, benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium (PyBOP), 2-(1H-Benzotriazole-1yl)-1,1,3,3-tetramethyluronium hexaflurophosphate (HBTU) as well as O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium (HATU), (2) preformed active esters such as pentafluorophenyl (Opfp), (3) preformed symmetrical anhydrides, and (4) acid halides such as acyl fluoride as well as acyl chloride.
Octreotide and Octreotide-derived delivery systems
Published in Journal of Drug Targeting, 2023
Mingliang Fan, Yue Huang, Xinlin Zhu, Jiayu Zheng, Mingwei Du
As an antimicrotubule chemotherapeutic agent, paclitaxel (PTX) inhibits microtubule depolymerisation and interferences with cell cycle to induce cell death. PTX is often structurally modified at the 2′ or 7 position to obtain conjugates with additional features (Figure 3). Huang et al. synthesised OCT-PTX by coupling succinylated PTX (at 2′-hydroxl group) to α amino group in the Phe1 of OCT on the resin. PTX 2′-succinate is activated by PyBOP (Benzotriazol-1-yl-oxytripyrrolidino-phosphonium hexaflorophosphate) in the reaction (Figure 4). In vitro assays showed that OCT-PTX retains the biological activities of PTX and can trigger cell apoptosis in a SSTR dependent way [53]. Wang’s group prepared PTX-OCT and 2PTX-OCT by linking one or two molecules of succinylated PTX to one molecule of OCT, these conjugates specifically inhibited cellular growth in SSTR-expressed human non-small lung cancer A549 and Calu-6 cell lines. The antitumor effects of these conjugates were further investigated in A549 cells xenografted into nude mice, 2PTX-OCT was more effective to inhibit tumour growth and less toxic in comparison to PTX. PTX-OCT was less potent in tumour growth inhibition than 2PTX-OCT administered at equimolar dose [54,55].
Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model
Published in OncoImmunology, 2020
Pravin T. P. Kaumaya, Linlin Guo, Jay Overholser, Manuel L. Penichet, Tanios Bekaii-Saab
Four novel peptide sequences that were identified to target human PD-1 were synthesized using a 9600 Milligen/Biosearch solid-phase peptide synthesizer (Millipore, Bedford, MA, USA) with Fmoc/t-Butyl chemistry and PyBOP/6Cl-HOBT coupling reagents on CLEAR amide resin (Peptides International, Louisville, KY, USA). Some peptide samples were acetylated using 1-Acetylimidazole (Sigma-Aldrich St. Louis, MO, USA) before cleavage to provide samples of peptides with more stable configuration as compared to free peptides which display flexible conformation. All peptides were synthesized as chimeric constructs with a “promiscuous” T helper epitope derived from the measles virus fusion protein (MVF, amino acids 288–302) using a four-residue linker (GPSL). Peptides were cleaved from the resin using cleavage reagent R (TFA)/thioanisole/EDT/anisole (90/5/3/2), and crude peptides were purified by semi preparative (C-4 Vydac columns) reversed-phase-high performance liquid chromatography (RP-HPLC; Waters, Bedford, MA, USA). RP-HPLC fractions showing the same retention time were pooled together and lyophilized. All peptides showed purity in excess of 95%. Samples were then characterized by MALDI (Matrix-Assisted Laser Desorption Ionization) mass spectroscopy at the CCIC (Campus Chemical Instrumentation Center, The Ohio State University, Columbus, OH, USA) and analyzed on an analytical RP-HPLC system (Waters, Bedford, MA, USA). All peptides had the correct molecular mass.
Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
José Teixeira, Catarina Oliveira, Fernando Cagide, Ricardo Amorim, Jorge Garrido, Fernanda Borges, Paulo J. Oliveira
Synthesis of [5–(6-(3,4,5-trimethoxybenzamido)hexylamino)carbonylpentyl] triphenylphosphonium bromide (6). To a solution of compound 4 (689 mg, 2.2 mmol) in DMF (7.4 ml) at 4 °C N,N-diethylpropan-2-amine (0.476 ml, 2.7 mmol) and PyBOP (1572 mg, 2.7 mmol) in CH2Cl2 (7.4 ml) were added. The mixture was kept in an ice bath and stirred for half hour. After this period, compound 5 (1218, 2.7 mmol) was added and then the reaction was heated up to room temperature. The reaction was kept under stirring for 20 h. The mixture was then diluted with AcOEt (40 ml) and washed with saturated NaHCO3 solution (2 × 10 ml). The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (10% MeOH/CH2Cl2), yield: 63%.