Abstract:
:Structural modification of naturally occurring beta-lactams and beta-lactones is a highly effective strategy for generating drugs for treating bacterial infections, cancer, obesity, and hyperlipidemia. These drugs acylate catalytic amino acids (serine, threonine, or cysteine) in enzyme targets such as penicillin-binding proteins (PBPs), beta-lactamases, lipases, HMG-CoA reductase, fatty acid synthetase, and the 20S proteasome. Optimally performing drugs combine features of high target affinity, chemoselective reactivity, and high stability of the acylated target protein. This review provides a perspective on these two classes of acylating agents and summarizes recent advances in mechanism and structure-based design of acylating drugs.
journal_name
Curr Opin Chem Bioljournal_title
Current opinion in chemical biologyauthors
Kluge AF,Petter RCdoi
10.1016/j.cbpa.2010.03.035subject
Has Abstractpub_date
2010-06-01 00:00:00pages
421-7issue
3eissn
1367-5931issn
1879-0402pii
S1367-5931(10)00051-7journal_volume
14pub_type
杂志文章,评审abstract::The site specific, co-translational introduction of unnatural amino acids into proteins produced in cells has been facilitated by the development of the pyrrolysyl-tRNA synthetase/tRNACUA pair. This pair can now be used to direct the site-specific incorporation of designer amino acids in E. coli, yeast, mammalian cell...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2014.07.001
更新日期:2014-08-01 00:00:00
abstract::There is growing interest in the design of synthetic molecules that mimic the structures and functions of epitopes found on the surface of peptides and proteins. Epitope mimetics can provide valuable tools to probe complex biological processes, as well as interesting leads for drug and vaccine discovery. One applicati...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2011.02.015
更新日期:2011-06-01 00:00:00
abstract::RNA plays an essential cellular role in nearly every aspect of the transmission and expression of genetic information, including regulatory roles that have significance for cellular development. Access to RNA bearing synthetic modifications has allowed biological chemists to probe deep into the inner workings of cellu...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2005.10.009
更新日期:2005-12-01 00:00:00
abstract::Aside from the demonstration that individual molecular traits of enzymes can be evolutionarily optimised, the discovery that several traits can be simultaneously optimised is a major advance. The first observations of the effects of evolutionary optimisation at the structural level, through X-ray crystallography, rein...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00087-9
更新日期:2000-06-01 00:00:00
abstract::Small molecule production in microbial hosts is limited by the accumulation of the product inside the cell. Efflux transporters show promise as a solution to removal of the often-toxic products. Recent advances in transporter identification through expression profiling, heterologous expression, and knockout studies ha...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2015.05.019
更新日期:2015-10-01 00:00:00
abstract::Nucleic acids such as DNA are increasingly being applied in nanotechnology, as a result of their capability to self-assemble reversibly. The formal replacement of canonical base pairs by metal-mediated ones enables a site-specific introduction of metal-based functionality into these biomolecules, leading to the format...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2017.01.019
更新日期:2017-04-01 00:00:00
abstract::The introduction of fluorine atoms into organic molecules has received considerable attention as these organofluorines have often found widespread applications in bioorganic chemistry, medicinal chemistry and biomaterial science. Despite innovation of synthetic C-F forming methodologies, selective fluorination is stil...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2020.01.004
更新日期:2020-04-01 00:00:00
abstract::The first photocaged complexes appeared in the mid-1980s specifically to complement the ongoing work studying intracellular Ca(2+) signaling with fluorescent probes. Recently, the field of biological inorganic chemistry has focused increasingly on the homeostasis mechanisms and possible signaling functions of transiti...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2012.11.015
更新日期:2013-04-01 00:00:00
abstract::Inflammatory and autoimmune diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, psoriasis and asthma, provide drug discoverers with a tremendous challenge. The precise causes of these diseases are not known, but our understanding of the molecular and cellular mechanisms associate...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/S1367-5931(99)80071-4
更新日期:1999-08-01 00:00:00
abstract::The fermentation of synthesis gas (including carbon monoxide, carbon dioxide, and hydrogen) with anaerobic acetogens is an established biotechnological process that has recently been transferred to a commercial scale. The natural product spectrum of acetogens is natively restricted to acetate, ethanol, and 2,3-butaned...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2017.10.003
更新日期:2017-12-01 00:00:00
abstract::The notorious difficulty of elucidating structures of membrane transporters by crystallography has long prevented our understanding of active transport mechanism coupled with ion/proton transport. The determination of the first crystal structure of the drug/H+ antiporter AcrB was a breakthrough for structure-based und...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2003.08.014
更新日期:2003-10-01 00:00:00
abstract::Natural evolution has produced a great diversity of proteins that can be harnessed for numerous applications in biotechnology and pharmaceutical science. Commonly, specific applications require proteins to be tailored by protein engineering. Directed evolution is a type of protein engineering that yields proteins with...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2014.09.013
更新日期:2014-10-01 00:00:00
abstract::There is tremendous interest in developing and refining methods to predictably perform chemical reactions within the framework of living systems. Here we review recent advances in applying tetrazine cycloadditions to live cell and in vivo chemistry. We highlight new syntheses of the tetrazine and dienophile precursors...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2013.08.004
更新日期:2013-10-01 00:00:00
abstract::To improve the deconstruction of biomass, the most abundant terrestrial source of carbon polymers, en route to renewable fuels, chemicals, and materials more knowledge is needed into the mechanistic interplay between thermochemical pretreatment and enzymatic hydrolysis. In this review we highlight recent progress in a...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2015.08.014
更新日期:2015-12-01 00:00:00
abstract::Because biomarkers are typically low in abundance, the crucial step of biomarker discovery is to efficiently separate clinically relevant sets of proteins that might define disease stages and/or predict disease development. It is anticipated that a multi-dimensional fractionation system (MDFS) will provide an efficien...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2006.01.007
更新日期:2006-02-01 00:00:00
abstract::To transfer to the laboratory, the excellent efficiency shown by enzymes in Nature, biocatalysis, had to mimic several synthetic strategies used by the living organisms. Biosynthetic pathways are examples of tandem catalysis and may be assimilated in the biocatalysis field for the use of isolated multi-enzyme systems ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2013.02.015
更新日期:2013-04-01 00:00:00
abstract::Nitrogenase catalyzes the important reactions of N2-reduction, CO-reduction and CO2-reduction at its active cofactor site. Designated the M-cluster, this complex metallocofactor is assembled through the generation of a characteristic 8Fe-core before the insertion of Mo and homocitrate that completes the stoichiometry ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2016.02.016
更新日期:2016-04-01 00:00:00
abstract::Due to the existence of numerous isomers, the in-depth analysis of glycans represents a major challenge. Currently, the majority of glycans are analysed using mass spectrometry (MS)-based techniques, which can provide information on regioisomers but usually fail to differentiate stereoisomers. A promising approach to ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2017.10.021
更新日期:2018-02-01 00:00:00
abstract::The asymmetric bioreduction of alkenes bearing an electron-withdrawing group using flavin-dependent enzymes from the 'old yellow enzyme' family at the expense of NAD(P)H yields the corresponding non-racemic alkanes going in hand with the creation of up to two chiral carbon centres. To avoid external cofactor recycling...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2007.02.025
更新日期:2007-04-01 00:00:00
abstract::Peptides that recognize specific cell types promise to be valuable tools both in research and clinical applications. Cell-specific peptides can be useful as drug delivery vehicles, diagnostic agents, affinity reagents for cell purification, gene therapy delivery agents, and research tools to probe the nature of a cell...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(99)00045-9
更新日期:2000-02-01 00:00:00
abstract::Recent advances in -omic profiling technologies have ushered in an era where we no longer want to merely measure the presence or absence of a biomolecule of interest, but instead hope to understand its function and interactions within larger signaling networks. Here, we review several emerging proteomic technologies c...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2020.02.001
更新日期:2020-02-01 00:00:00
abstract::Functional amino acids that play critical roles in catalysis and regulation are known to display elevated nucleophilicity and can be selectively targeted for covalent modification by reactive electrophiles. Chemical-proteomic platforms, such as activity-based protein profiling (ABPP), exploit this reactivity by utiliz...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2014.10.021
更新日期:2015-02-01 00:00:00
abstract::Numerous developments in useful linkers are closely related with the advances in solid-phase organic synthesis. These linkers allow facile attachment functionalization and release molecules of interest. Designing a new anchoring group can be essential for synthesis success, especially for small molecules on solid supp...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2004.04.004
更新日期:2004-06-01 00:00:00
abstract::A variety of protein sequence databases exist, ranging from simple sequence repositories, which store data with little or no manual intervention in the creation of the records, to expertly curated universal databases that cover all species and in which the original sequence data are enhanced by the manual addition of ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2003.12.004
更新日期:2004-02-01 00:00:00
abstract::During the past year, remarkable progress has been made in understanding how periplasmic chaperones fold and protect protein modules that are destined for assembly into adhesive pili in Gram-negative bacteria. The first two three-dimensional structures of complexes of periplasmic chaperones with substrate pilus subuni...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/s1367-5931(00)00144-7
更新日期:2000-12-01 00:00:00
abstract::Signal amplification in conventional enzyme-based biosensors is not high enough to achieve the ultrasensitive detection of biomolecules. In recent years, signal amplification has been improved by combining enzymatic reactions with redox cycling or employing multienzyme labels per detection probe. Electrochemical-chemi...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2012.03.015
更新日期:2012-08-01 00:00:00
abstract::Numerous tools for Zn2+ sensing in living cells have become available in the past three years. Among them, fluorescence imaging using fluorescent sensor molecules has been the most popular approach. Some of these sensor molecules can be used to visualize Zn2+ in living cells. Some of the biological functions of Zn2+ h...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2004.02.007
更新日期:2004-04-01 00:00:00
abstract::Synthetic biology offers a bottom-up engineering approach that intends to understand complex systems via design-build-test cycles. Embryonic development comprises complex processes that originate at the level of gene regulatory networks in a cell and emerge into collective cellular behaviors with multicellular forms a...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2019.04.006
更新日期:2019-10-01 00:00:00
abstract::Initiating and terminating free-radical reactionis via hydrogen atom transfer (HAT) is an attractive means of avoiding substrate prefunctionalization. Small molecule catalysts and reagents, however, struggle to execute this fundamental step with useful levels of diastereoselectivity and enantioselectivity. In contrast...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2018.09.001
更新日期:2019-04-01 00:00:00
abstract::Protein-polymer conjugates are of interest to researchers in diverse fields. Attachment of polymers to proteins results in improved pharmacokinetics, which is important in medicine. From an engineering standpoint, conjugates are exciting because they exhibit properties of both the biomolecules and synthetic polymers. ...
journal_title:Current opinion in chemical biology
pub_type: 杂志文章,评审
doi:10.1016/j.cbpa.2010.10.008
更新日期:2010-12-01 00:00:00