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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.
Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Rui Chen, Zhongyuan Wang, Lijie Sima, Hu Cheng, Bilan Luo, Jianta Wang, Bing Guo, Shunyi Mao, Zhixu Zhou, Jingang Peng, Lei Tang, Xinfu Liu, Weike Liao
As depicted in Scheme 1, a simple five-step synthetic sequence was used for the preparation of compounds described herein. Firstly, 2-aminopyridine derivatives and N-Bromosuccinimide (NBS) undergo electrophilic aromatic substitution reaction in the presence of DMF to obtain 2-amino-3-bromo-pyridine derivatives (11a-b), 11a-b and commercially available 3-bromopyridin-2-amine were then cyclized with ethyl 3-bromopyruvate to give the ethyl 8-bromo-Imidazo[1,2-a]pyridine-2-carboxylate derivatives (12a-c). Intermediates 12a-c were further hydrolysed by NaOH to offer the corresponding carboxylic acids (13a-c). Subsequently, the key intermediates 14a-h were synthesised through amidation reaction of 13a-c with various amines and coupling reagent HBTU in DMF. Finally, compounds 14a-h undergo Suzuki-Miyaura reaction with the corresponding boronic acids or esters (9a-c) to obtain the corresponding target products 15–46. The chemical structures of the target compounds were confirmed with HRMS, 1H NMR, and 13C NMR.
PEGylated pH-responsive peptide-mRNA nano self-assemblies enhance the pulmonary delivery efficiency and safety of aerosolized mRNA
Published in Drug Delivery, 2023
Yingying Xu, Yijing Zheng, Xuqiu Ding, Chengyan Wang, Bin Hua, Shilian Hong, Xiaoman Huang, Jiali Lin, Peng Zhang, Wei Chen
Polypeptides were synthesized by Fmoc solid phase synthesis method by Rink amide-MBHA Resin. Some potential active sites of the LA polypeptide chain were chemically protected before PEGylation, including the histidine, protected by the Trt group, and the Boc group, protected by the lysine. The leucine and alanine side chains were not chemically protected since no reactive functional groups existed. Afterward, the N-terminal amino group of the LA peptide was connected with a monodisperse PEG of different polymerization degrees by dehydration condensation. Specifically, 1.5 eq Boc-NH2-PEG12-CH2CH2COOH was dissolved in DMF, then 3 eq HBTU and 10 eq DIEA were added and reacted for 60 min at room temperature. PEG12/PEG24 modified LAH4-L1 polypeptide was obtained by lysing TFA/TIS/H2O/EDT (92.5:2.5:2.5:2.5% v/v) for 2 h at room temperature and precipitated by ether. The products were purified by HPLC and lyophilized. The purity of PEG-modified polypeptides was verified by HPLC (purity > 90%), and their molecular weight was confirmed by ESI-MS.
Transferrin receptor targeting segment T7 containing peptide gene delivery vectors for efficient transfection of brain tumor cells
Published in Drug Delivery, 2022
Ziyao Kang, Chunlan Zeng, Long Tian, Taoran Wang, Sen Yang, Qin Cheng, Jing Zhang, Qingbin Meng, Changhao Zhang, Zhao Meng
All peptides were synthesized using a Liberty automated microwave peptide synthesizer (CEM Co., Matthews, NC) together with a standard solid-phase Fmoc chemistry protocol. Rink amide resin with a loading capacity of 0.44 mmol/g was used as a solid phase to obtain C-terminally amidated peptides. Coupling of the amino acids was achieved using HBTU in DMF as an activator and DIEA in NMP as an active base. A 20% (v/v) solution of piperidine in DMF was added to the resin for deprotection. After every coupling or deprotection, the resin was washed with DMF and DCM for three times respect. Amino acids were individually coupled to Rink amide resin, followed by the amino group in the side chain of lysine conjugation of stearic acid. Final cleavage was performed with 10 mL of TFA (90%)/thioanisole (5%)/ethanedithiol (3%)/anisole (2%) for 3 h at room temperature. The products were purified by preparative reverse-phase high-performance liquid chromatography (RP-HPLC) using a C8 column (Waters, USA). All peptides were purified to >95% purity. The molecular weights (MWs) of the peptides were determined by Electrospray Ionization Quadrupole-Time of Flight mass spectrometry (MALDI-TOF-MS; Waters Micromass Q-TOF Micro Mass Spectrometer).