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991.
Design of S‐Allylcysteine in Situ Production and Incorporation Based on a Novel Pyrrolysyl‐tRNA Synthetase Variant 下载免费PDF全文
Dr. Matthias P. Exner Tilmann Kuenzl Tuyet Mai T. To Zhaofei Ouyang Sergej Schwagerus Michael G. Hoesl Prof. Dr. Christian P. R. Hackenberger Prof. Dr. Marga C. Lensen Prof. Dr. Sven Panke Prof. Dr. Nediljko Budisa 《Chembiochem : a European journal of chemical biology》2017,18(1):85-90
The noncanonical amino acid S‐allyl cysteine (Sac) is one of the major compounds of garlic extract and exhibits a range of biological activities. It is also a small bioorthogonal alkene tag capable of undergoing controlled chemical modifications, such as photoinduced thiol‐ene coupling or Pd‐mediated deprotection. Its small size guarantees minimal interference with protein structure and function. Here, we report a simple protocol efficiently to couple in‐situ semisynthetic biosynthesis of Sac and its incorporation into proteins in response to amber (UAG) stop codons. We exploited the exceptional malleability of pyrrolysyl‐tRNA synthetase (PylRS) and evolved an S‐allylcysteinyl‐tRNA synthetase (SacRS) capable of specifically accepting the small, polar amino acid instead of its long and bulky aliphatic natural substrate. We succeeded in generating a novel and inexpensive strategy for the incorporation of a functionally versatile amino acid. This will help in the conversion of orthogonal translation from a standard technique in academic research to industrial biotechnology. 相似文献
992.
Iterative Nonproteinogenic Residue Incorporation Yields α/β‐Peptides with a Helix–Loop–Helix Tertiary Structure and High Affinity for VEGF 下载免费PDF全文
Dr. James W. Checco Prof. Samuel H. Gellman 《Chembiochem : a European journal of chemical biology》2017,18(3):291-299
Inhibition of specific protein–protein interactions is attractive for a range of therapeutic applications, but the large and irregularly shaped contact surfaces involved in many such interactions make it challenging to design synthetic antagonists. Here, we describe the development of backbone‐modified peptides containing both α‐ and β‐amino acid residues (α/β‐peptides) that target the receptor‐binding surface of vascular endothelial growth factor (VEGF). Our approach is based on the Z‐domain, which adopts a three‐helix bundle tertiary structure. We show how a two‐helix “mini‐Z‐domain” can be modified to contain β and other nonproteinogenic residues while retaining the target‐binding epitope by using iterative unnatural residue incorporation. The resulting α/β‐peptides are less susceptible to proteolysis than is their parent α‐peptide, and some of these α/β‐peptides match the full‐length Z‐domain in terms of affinity for receptor‐recognition surfaces on the VEGF homodimer. 相似文献
993.
Paolo Schiavini Kin J. Cheong Prof. Nicolas Moitessier Prof. Karine Auclair 《Chembiochem : a European journal of chemical biology》2017,18(3):248-252
Substrate‐promiscuous enzymes are a promising starting point for the development of versatile biocatalysts. In this study, human cytochrome P450 3A4, known for its ability to metabolise hundreds of drugs, was engineered to alter its regio‐ and stereoselectivity. Rational mutagenesis was used to introduce steric hindrance in a specific manner in the large active site of P450 3A4 and to favour oxidation at a more sterically accessible position on the substrate. Hydroxylation of a synthetic precursor of (R)‐lisofylline, a compound under investigation for its anti‐inflammatory properties, was chosen as a first proof‐of‐principle application of our protein engineering strategy. In a second example, increasing active site crowding led to an incremental shift in the selectivity of oxidation from an internal double bond to a terminal phenyl group in a derivative of theobromine. The same correlation between crowding and selectivity was found in a final case focused on the hydroxylation of the steroid sex hormone progesterone. 相似文献
994.
Chemical Synthesis of K34‐Ubiquitylated H2B for Nucleosome Reconstitution and Single‐Particle Cryo‐Electron Microscopy Structural Analysis 下载免费PDF全文
Jiabin Li Qiaoqiao He Yuntao Liu Sanling Liu Shan Tang Chengmin Li Demeng Sun Xiaorun Li Min Zhou Ping Zhu Guoqiang Bi Prof. Zhenghong Zhou Ji‐Shen Zheng Prof. Changlin Tian 《Chembiochem : a European journal of chemical biology》2017,18(2):176-180
Post‐translational modifications (e.g., ubiquitylation) of histones play important roles in dynamic regulation of chromatin. Histone ubiquitylation has been speculated to directly influence the structure and dynamics of nucleosomes. However, structural information for ubiquitylated nucleosomes is still lacking. Here we report an alternative strategy for total chemical synthesis of homogenous histone H2B‐K34‐ubiquitylation (H2B‐K34Ub) by using acid‐cleavable auxiliary‐mediated ligation of peptide hydrazides for site‐specific ubiquitylation. Synthetic H2B‐K34Ub was efficiently incorporated into nucleosomes and further used for single‐particle cryo‐electron microscopy (cryo‐EM) imaging. The cryo‐EM structure of the nucleosome containing H2B‐K34Ub suggests that two flexible ubiquitin domains protrude between the DNA chains of the nucleosomes. The DNA chains around the H2B‐K34 sites shift and provide more space for ubiquitin to protrude. These analyses indicated local and slight structural influences on the nucleosome with ubiquitylation at the H2B‐K34 site. 相似文献
995.
996.
Different Enzymatic Processing of γ‐Phosphoramidate and γ‐Phosphoester‐Modified ATP Analogues 下载免费PDF全文
Susanne Ermert Dr. Stephan M. Hacker Dr. Alexander Buntru Prof. Dr. Martin Scheffner Prof. Dr. Christof R. Hauck Prof. Dr. Andreas Marx 《Chembiochem : a European journal of chemical biology》2017,18(4):378-381
Monitoring the activity of ATP‐consuming enzymes provides the basis for elucidating their modes of action and regulation. Although a number of ATP analogues have been developed for this, their scope is restricted because of the limited acceptance by respective enzymes. In order to clarify which kind of phosphate‐modified ATP analogues are accepted by the α‐β‐phosphoanhydride‐cleaving ubiquitin‐activating enzyme 1 (UBA1) and the β‐γ‐phosphoanhydride‐cleaving focal adhesion kinase (FAK), we tested phosphoramidate‐ and phosphoester‐modified ATP analogues. UBA1 and FAK were able to convert phosphoramidate‐modified ATP analogues, even with a bulky modification like biotin. In contrast, a phosphoester‐modified analogue was poorly accepted. These results demonstrate that minor variations in the design of ATP analogues for monitoring ATP utilization have a significant impact on enzymatic acceptance. 相似文献
997.
Dr. Riccardo Martini Dr. Francesca Esposito Dr. Angela Corona Dr. Roberto Ferrarese Dr. Elisa Rita Ceresola Dr. Laura Visconti Dr. Cristina Tintori Dr. Alessandro Barbieri Dr. Andrea Calcaterra Dr. Valentina Iovine Dr. Filippo Canducci Prof. Enzo Tramontano Prof. Maurizio Botta 《Chembiochem : a European journal of chemical biology》2017,18(4):374-377
998.
999.
Dr. Christina Haußner Dominik Damm Sandra Nirschl Anette Rohrhofer Prof. Dr. Barbara Schmidt Prof. Dr. Jutta Eichler 《Chembiochem : a European journal of chemical biology》2017,18(7):647-653
The broadly neutralizing HIV‐1 antibody b12 recognizes the CD4 binding site of the HIV‐1 envelope glycoprotein gp120 and efficiently neutralizes HIV‐1 infections in vitro and in vivo. Based on the 3D structure of a b12 ? gp120 complex, we have designed an assembled peptide (b12‐M) that presents the parts of the three heavy‐chain complementarity‐determining regions (CDRs) of b12, which contain the contact sites of the antibody for gp120. This b12‐mimetic peptide, as well as a truncated peptide presenting only two of the three heavy‐chain CDRs of b12, were shown to recognize gp120 in a similar manner to b12, as well as to inhibit HIV‐1 infection, demonstrating functional mimicry of b12 by the paratope mimetic peptides. 相似文献
1000.
Synthesis,Characterization and Immunological Evaluation of Self‐Adjuvanting Group A Streptococcal Vaccine Candidates Bearing Various Lipidic Adjuvanting Moieties 下载免费PDF全文
Dr. Vincent Fagan Dr. Waleed M. Hussein Mei Su Ashwini K. Giddam Dr. Michael R. Batzloff Prof. Michael F. Good Prof. Istvan Toth Dr. Pavla Simerska 《Chembiochem : a European journal of chemical biology》2017,18(6):545-553
Four group A streptococcal glycolipopeptide vaccine candidates with different lipidic adjuvanting moieties were prepared and characterized. The immunogenicity of the compounds was evaluated by macrophage and dendritic cell uptake studies and by in vivo quantification of systemic IgG antibody by ELISA. Three of the candidates showed significant induction of the IgG response. 相似文献