Cyclic peptides from unprotected precursors through ring-chain tautomerism (original) (raw)
Related papers
N-urethane protected carboxyanhydrides (UNCAs) in amino acid and peptide chemistry
Chinese Peptide Symposia, 2002
The fourth Chinese Peptide Symposium, hosted by Peking University, was held at Chengdu, China on July 21-25, 1996 with 164 participants, including 45 scientists from abroad, representing 12 countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-96 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 10 sessions with 55 oral and 78 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistrybiology-interface and challenging problems in peptides. The enthusiastic cooperation and excellent contributions were gratifying and the active response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. James P. Tam and Dr. Jie-Cheng Xu were the recipients of 'The Cathay Award' sponsored by the H. H. Liu Education Foundation, offered for their seminal contributions in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group). It is our pleasure to acknowledge Nobel Laureate Professor Bruce R. Merrifield for his kindness in supporting and serving as the chairman of the Awarding Committee for the 'Cathay Award', and all members of the program and organizing committee for their generous contributions to the successful symposium. Dr. John R. Martin and Kluwer Academic Publishers kindly agreed to publish the CPS-96 proceedings, and we thank them for their contributions and support of the symposium.
Investigation of enzyme activity and inhibition in the interior of novel solid supports
Chinese Peptide Symposia, 2002
with 156 participants, including 30 scientists from abroad, representing nine countries. The four-day conference was both intense and spiritually rewarding. Our goal for CPS-98 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 8 sessions with 42 oral and 90 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand-receptor interactions, the chemistry-biology-interface and challenging problems in peptides.
Side reactions in the SPPS of Cys-containing peptides
Amino Acids, 2013
Alkylation of sensitive amino acids during synthesis of biologically important peptides is a common and well-documented problem in Fmoc-based strategy. Herein, we probed for the first time an unexpected S-alkylation of Cys-containing peptides that occur during the final TFA cleavage of peptides from the Wang solid support. Through a battery of approaches (NMR, UV and LC-MS) the formed by-product was assigned as the alkylation of the cysteine sulfydryl group by the p-hydroxyl benzyl group derived from the acidic Wang linker decomposition. Factors affecting this side reaction were monitored and a protocol that minimizes the presence of the by-product is reported.
J. Am. Chem. Soc. 2012, 134, 4661−4669(G. Basu)
Although weak interactions play subtle but important roles in dictating protein structures, their experimental detection is nontrivial. From NOE experiments we provide direct evidence for the presence of CH···π interaction, operational between the C α -H of the first Pro and the aromatic (Aro) side chain of Xaa, in a peptide series with the general sequence Ac-Pro-Pro-Xaa-NH 2 . Indirect evidence of CH···π interaction is provided from ring current-induced upfield displacement of Pro(1) C α -H chemical shifts and restriction of sidechain (χ1) rotation of Xaa. A consequence of this interaction is the enhanced stability of the Pro-cisPro conformer in Ac-Pro-Pro-Xaa-NH 2 when Xaa is aromatic. The free energies associated with trans to cis transformation of the Pro-Pro moiety are 0.35, 0.59, 0.64, and 0.82 kcal/mol when Xaa is Tyr, Trp, Phe, and His (pH of 8.4), respectively. In comparison, the corresponding free energy is ∼1.55 kcal/mol when Xaa is nonaromatic. The observed population of Pro-cisPro-His and the pH-induced perturbation of electron density of the His side chain were correlated, providing further evidence for a direct role of CH···π interaction in modulating the stability of Pro-cisPro population in Ac-Pro-Pro-Aro-NH 2 . Our study establishes Pro-Pro-Aro to be a new sequence motif that can stabilize Pro-cisPro peptide bonds. This study not only identifies a new structurally biased sequence motif but also directly demonstrates the role played by CH···π interactions in subtly altering conformational preferences of three-residue peptide sequences with implications on the role played by cis-peptide bonds in unfolded proteins.
The Journal of Organic Chemistry, 2006
S-2 1. General Procedure for the Buchwald-Hartwig Cyclization Reaction. rac-BINAP (40 mol%) was added to HPLC grade acetonitirle (1.5x10-3 M) solvent and solution refluxed for 30 min. Allowed to room temperature and the palladium acetate (30 mol%) was added and stirred for 15 min, followed by acyclic peptide (500 mg) and finally the base Cs 2 CO 3 (4eq) were added. The resulting reaction mixture was stirred at 100 o C for 15 h. After this period of stirring, the solvent was removed under reduced pressure, and the residue was subsequently purified by column chromatography. 2. General Procedure for the Buchwald-Hartwig Cyclization Reaction. rac-BINAP (40 mol%) was added to HPLC grade acetonitirle (1.5x10-3 M) solvent and solution refluxed for 30 min. Allowed to room temperature and the palladium acetate (30 mol%) was added and stirred for 15 min, followed by acyclic peptide (500 mg) and finally the base t BuOK (2eq) were added. The resulting reaction mixture was stirred at 100 o C for 15 h. After this period of stirring, the solvent was removed under reduced pressure, and the residue was subsequently purified by column chromatography. 3. General Procedure for peptide coupling. (a) To a stirred solution of the TFA salt of C-protected peptide in CH 2 Cl 2 (5 mL/mmol) at 0 o (ice-bath) under N 2 was treated successively with Et 3 N (5 equiv), HOBt (1.2 equiv), a solution of the Boc-protected amino acid (1 equiv) in CH 2 Cl 2 (2.5 mL/mmol), and EDC (1.2 equiv). The mixture was allowed to warm to r.t., and stirring was continued for 15 h. The mixture was diluted with CH 2 Cl 2 and washed with 10% aq. citric acid, aq. saturated NaHCO 3 , H 2 O and saturated NaCl solution. The organic phase was dried (Na 2 SO 4), evaporated, and the residue was purified using flash column chromatography to get the pure material. S-3 (b) To a stirred solution of TFA salt of C-protected peptide in CH 2 Cl 2 (3 mL/mmol) and DMF (2 mL/mmol) at 0 o (ice-bath) under N 2 was treated successively with Et 3 N (5 equiv), HOBt (1.2 equiv), a solution of the Boc-protected amino acid (1 equiv) in CH 2 Cl 2 (2.5 mL/mmol), and EDC (1.2 equiv). The mixture was allowed to warm to r.t., and stirring was continued for 15 h. The residue obtained after the removal of all volatiles was dried under vacuum for 1 h and then stirred in MeOH for 20 min. The white precipitate was collected by filtration and thoroughly washed with MeOH/H 2 O 1:1 mixture. The solid product was dried under high vacuum for several hours. 4. General procedure for Boc deprotection. (a) CF 3 COOH (1.5 mL/mmol) was added to an ice-cold solution of the Boc-protected peptide in CH 2 Cl 2 (5 mL/mmol). The reaction mixture was allowed to warm to r.t. and stirring was continued for 2 h. The mixture was evaporated and the residue dried under high vaccum. The salts with CF 3 COOH were used without further purification and characterization. (b) CF 3 COOH (1.5 mL/mmol) was added to an ice-cold solution of the Boc-protected peptide in CH 2 Cl 2 (5 mL/mmol). The reaction mixture was allowed to warm to r.t. and stirring was continued for 3 h. The mixture was evaporated and the residue dried under high vaccum. Then the residue dissolved in mixture of DCM and DMF solution and basified (PH-8) with Et 3 N. The mixture solution was concentrated to its 1/3 volume and 1:1 Methanol and water solution added. Solid compound was obtained on stirring for 30 min at room temperature. Filtered off and dried under vaccum for 6-10 h.
PROCEEDINGS OF THE MERCK & ELSEVIER YOUNG CHEMISTSSYMPOSIUM
2018
Welcome message Dear participants, welcome to the 18 th edition of the Merck & Elsevier Young Chemists Symposium, formerly SAYCS and MYCS. This conference is an international scientific event organized by the Young Group of the Italian Chemical Society (SCI Giovani) with the financial support of Merck and Elsevier. This symposium is fully devoted to young researchers, such as MSc and PhD students, post-doc fellows and young researchers in companies. All the disciplines of Chemistry are covered: analytical, physical, industrial, organic, inorganic, theoretical, pharmaceutical, biological, environmental, macromolecular and electrochemistry. This year, a special emphasis will be given to chemistry from knowledge to innovation: how chemistry is increasingly present in all of the fields that are essential for human life, and how chemical fundamentals are pushing novel technologies? This year we have the exceptional number of 212 participants; we thank you for the great trust shown towards SCI Giovani, Merck and Elsevier. Enjoy the conference!