Template-constrained macrocyclic peptides prepared from native, unprotected precursors.

Abstract:

:Peptide-protein interactions are important mediators of cellular-signaling events. Consensus binding motifs (also known as short linear motifs) within these contacts underpin molecular recognition, yet have poor pharmacological properties as discrete species. Here, we present methods to transform intact peptides into stable, templated macrocycles. Two simple steps install the template. The key reaction is a palladium-catalyzed macrocyclization. The catalysis has broad scope and efficiently forms large rings by engaging native peptide functionality including phenols, imidazoles, amines, and carboxylic acids without the necessity of protecting groups. The tunable reactivity of the template gives the process special utility. Defined changes in reaction conditions markedly alter chemoselectivity. In all cases examined, cyclization occurs rapidly and in high yield at room temperature, regardless of peptide composition or chain length. We show that conformational restraints imparted by the template stabilize secondary structure and enhance proteolytic stability in vitro. Palladium-catalyzed internal cinnamylation is a strong complement to existing methods for peptide modification.

authors

Lawson KV,Rose TE,Harran PG

doi

10.1073/pnas.1311706110

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

E3753-60

issue

40

eissn

0027-8424

issn

1091-6490

pii

1311706110

journal_volume

110

pub_type

杂志文章
  • Frequency of DNA end joining in trans is not determined by the predamage spatial proximity of double-strand breaks in yeast.

    abstract::DNA double-strand breaks (DSBs) are serious genomic insults that can lead to chromosomal rearrangements if repaired incorrectly. To gain insight into the nuclear mechanisms contributing to these rearrangements, we developed an assay in yeast to measure cis (same site) vs. trans (different site) repair for the majority...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1818595116

    authors: Sunder S,Wilson TE

    更新日期:2019-05-07 00:00:00

  • Cloning and sequencing of parafusin, a calcium-dependent exocytosis-related phosphoglycoprotein.

    abstract::A cDNA for parafusin, an evolutionarily conserved phosphoglycoprotein involved in exocytosis, has been cloned and sequenced from a unicellular eukaryote, Paramecium tetraurelia. A Paramecium cDNA library was screened with an oligonucleotide probe synthesized to an internal amino acid sequence of isolated parafusin. Th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.21.9832

    authors: Subramanian SV,Wyroba E,Andersen AP,Satir BH

    更新日期:1994-10-11 00:00:00

  • Does canvassing increase voter turnout? A field experiment.

    abstract::This paper reports the results of a randomized field experiment involving registered voters in the city of New Haven. Nonpartisan get-out-the-vote messages were delivered through personal canvassing shortly before the November 1998 election. We find that personal canvassing increased voter turnout by approximately 6. ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.19.10939

    authors: Gerber AS,Green DP

    更新日期:1999-09-14 00:00:00

  • Ca2+ current is regulated by cyclic GMP-dependent protein kinase in mammalian cardiac myocytes.

    abstract::Regulation of cardiac contraction by neurotransmitters and hormones is often correlated with regulation of the L-type Ca2(+)-channel current (ICa) through the opposite actions of two second messengers, cyclic AMP and cyclic GMP. While cyclic AMP stimulation of ICa is mediated by the activation of cyclic AMP-dependent ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.4.1197

    authors: Méry PF,Lohmann SM,Walter U,Fischmeister R

    更新日期:1991-02-15 00:00:00

  • Mutations that alter the transmission of chloroplast genes in Chlamydomonas.

    abstract::Two mutations are described that alter the pattern of inheritance of chloroplast genes in Chlamydomonas. The mutant gene mat-1 linked to the mating type allele mt(-) greatly increases the frequency of exceptional zygotes, i.e., zygotes that transmit chloroplast genes from the mt(-) (male) parent. In some crosses, 80-9...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.71.12.4698

    authors: Sager R,Ramanis Z

    更新日期:1974-12-01 00:00:00

  • Direct visualization of myosin-binding protein C bridging myosin and actin filaments in intact muscle.

    abstract::Myosin-binding protein C (MyBP-C) is a thick filament protein playing an essential role in muscle contraction, and MyBP-C mutations cause heart and skeletal muscle disease in millions worldwide. Despite its discovery 40 y ago, the mechanism of MyBP-C function remains unknown. In vitro studies suggest that MyBP-C could...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1103216108

    authors: Luther PK,Winkler H,Taylor K,Zoghbi ME,Craig R,Padrón R,Squire JM,Liu J

    更新日期:2011-07-12 00:00:00

  • In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation.

    abstract::Recent evidence implicates dysregulation of metabotropic glutamatergic receptor 5 (mGluR5) in pathophysiology of PTSD and suicidality. Using positron emission tomography and [18F]FPEB, we quantified mGluR5 availability in vivo in individuals with PTSD (n = 29) and MDD (n = 29) as a function of suicidal ideation (SI) t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1818871116

    authors: Davis MT,Hillmer A,Holmes SE,Pietrzak RH,DellaGioia N,Nabulsi N,Matuskey D,Angarita GA,Carson RE,Krystal JH,Esterlis I

    更新日期:2019-06-04 00:00:00

  • Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1.

    abstract::The long QT syndrome (LQTS) is a heritable disorder that predisposes to sudden cardiac death. LQTS is caused by mutations in ion channel genes including HERG and KCNE1, but the precise mechanisms remain unclear. To clarify this situation we injected adenoviral vectors expressing wild-type or LQT mutants of HERG and KC...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.091239098

    authors: Hoppe UC,Marbán E,Johns DC

    更新日期:2001-04-24 00:00:00

  • Mobile device data reveal the dynamics in a positive relationship between human mobility and COVID-19 infections.

    abstract::Accurately estimating human mobility and gauging its relationship with virus transmission is critical for the control of COVID-19 spreading. Using mobile device location data of over 100 million monthly active samples, we compute origin-destination travel demand and aggregate mobility inflow at each US county from Mar...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2010836117

    authors: Xiong C,Hu S,Yang M,Luo W,Zhang L

    更新日期:2020-11-03 00:00:00

  • Constructing, verifying, and dissecting the folding transition state of chymotrypsin inhibitor 2 with all-atom simulations.

    abstract::Experimentally, protein engineering and phi-value analysis is the method of choice to characterize the structure in folding transition state ensemble (TSE) of any protein. Combining experimental phi values and computer simulations has led to a deeper understanding of how proteins fold. In this report, we construct the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.241378398

    authors: Li L,Shakhnovich EI

    更新日期:2001-11-06 00:00:00

  • Origin of sphinx, a young chimeric RNA gene in Drosophila melanogaster.

    abstract::Non-protein-coding RNA genes play an important role in various biological processes. How new RNA genes originated and whether this process is controlled by similar evolutionary mechanisms for the origin of protein-coding genes remains unclear. A young chimeric RNA gene that we term sphinx (spx) provides the first insi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.072066399

    authors: Wang W,Brunet FG,Nevo E,Long M

    更新日期:2002-04-02 00:00:00

  • Present-day African analogue of a pre-European Amazonian floodplain fishery shows convergence in cultural niche construction.

    abstract::Erickson [Erickson CL (2000) Nature 408 (6809):190-193] interpreted features in seasonal floodplains in Bolivia's Beni savannas as vestiges of pre-European earthen fish weirs, postulating that they supported a productive, sustainable fishery that warranted cooperation in the construction and maintenance of perennial s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 历史文章,杂志文章

    doi:10.1073/pnas.1613169114

    authors: McKey DB,Durécu M,Pouilly M,Béarez P,Ovando A,Kalebe M,Huchzermeyer CF

    更新日期:2016-12-27 00:00:00

  • Liver-targeted disruption of Apc in mice activates beta-catenin signaling and leads to hepatocellular carcinomas.

    abstract::Although inappropriate activation of the Wnt/beta-catenin pathway has been implicated in the development of hepatocellular carcinoma (HCC), the role of this signaling in liver carcinogenesis remains unclear. To investigate this issue, we constructed a mutant mouse strain, Apc(lox/lox), in which exon 14 of the tumor-su...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0404761101

    authors: Colnot S,Decaens T,Niwa-Kawakita M,Godard C,Hamard G,Kahn A,Giovannini M,Perret C

    更新日期:2004-12-07 00:00:00

  • Nanoscopy through a plasmonic nanolens.

    abstract::Plasmonics now delivers sensors capable of detecting single molecules. The emission enhancements and nanometer-scale optical confinement achieved by these metallic nanostructures vastly increase spectroscopic sensitivity, enabling real-time tracking. However, the interaction of light with such nanostructures typically...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1914713117

    authors: Horton MJ,Ojambati OS,Chikkaraddy R,Deacon WM,Kongsuwan N,Demetriadou A,Hess O,Baumberg JJ

    更新日期:2020-02-04 00:00:00

  • An evolutionary scenario for the transition to undifferentiated multicellularity.

    abstract::The evolutionary transition from single cells toward multicellular forms of life represents one of the major transitions in the evolution of complex organisms. In this transition, single autonomously reproducing cells became parts of larger reproducing entities that eventually constituted a new unit of selection. The ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0335420100

    authors: Pfeiffer T,Bonhoeffer S

    更新日期:2003-02-04 00:00:00

  • Rapid solution assays for retroviral integration reactions and their use in kinetic analyses of wild-type and mutant Rous sarcoma virus integrases.

    abstract::A rapid method for quantitating products of the oligodeoxynucleotide processing reaction in vitro has been developed to facilitate enzymatic studies of the retroviral integrases. Unlike earlier procedures, this assay does not depend on polyacrylamide gel electrphoresis but separates products by batch adsorption to PEI...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.24.11633

    authors: Müller B,Jones KS,Merkel GW,Skalka AM

    更新日期:1993-12-15 00:00:00

  • MLCK-A, an unconventional myosin light chain kinase from Dictyostelium, is activated by a cGMP-dependent pathway.

    abstract::Dictyostelium myosin II is activated by phosphorylation of its regulatory light chain by myosin light chain kinase A (MLCK-A), an unconventional MLCK that is not regulated by Ca2+/calmodulin. MLCK-A is activated by autophosphorylation of threonine-289 outside of the catalytic domain and by phosphorylation of threonine...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.13000

    authors: Silveira LA,Smith JL,Tan JL,Spudich JA

    更新日期:1998-10-27 00:00:00

  • Interaction between a coating-borne peptide of the Brassica pollen grain and stigmatic S (self-incompatibility)-locus-specific glycoproteins.

    abstract::Methods are described for the removal of the sporophytic pollen grain coating of Brassica oleracea and for the isolation of coat polypeptides. The coat contains a small number of proteins ranging from 6 to 45 kDa. Many of the larger proteins are glycosylated, while all carry high positive charges resulting in pI value...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.2.467

    authors: Doughty J,Hedderson F,McCubbin A,Dickinson H

    更新日期:1993-01-15 00:00:00

  • A biosensor assay for studying ligand-membrane receptor interactions: binding of antibodies and HIV-1 Env to chemokine receptors.

    abstract::The HIV envelope (Env) protein mediates entry into cells by binding CD4 and an appropriate coreceptor, which triggers structural changes in Env that lead to fusion between the viral and cellular membranes. The major HIV-1 coreceptors are the seven transmembrane domain chemokine receptors CCR5 and CXCR4. The type of co...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.190274097

    authors: Hoffman TL,Canziani G,Jia L,Rucker J,Doms RW

    更新日期:2000-10-10 00:00:00

  • Subcellular localization of mineralocorticoid receptors in living cells: effects of receptor agonists and antagonists.

    abstract::Results on the subcellular localization of the mineralocorticoid receptor (MR) have been controversial. To determine the subcellular distribution and trafficking of the MR in living cells after binding of agonists and antagonists, we expressed a MR-green fluorescent protein (GFP) chimera in mammalian cells lacking end...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.6.2973

    authors: Fejes-Tóth G,Pearce D,Náray-Fejes-Tóth A

    更新日期:1998-03-17 00:00:00

  • The kuru infectious agent is a unique geographic isolate distinct from Creutzfeldt-Jakob disease and scrapie agents.

    abstract::Human sporadic Creutzfeldt-Jakob disease (sCJD), endemic sheep scrapie, and epidemic bovine spongiform encephalopathy (BSE) are caused by a related group of infectious agents. The new U.K. BSE agent spread to many species, including humans, and clarifying the origin, specificity, virulence, and diversity of these agen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905825106

    authors: Manuelidis L,Chakrabarty T,Miyazawa K,Nduom NA,Emmerling K

    更新日期:2009-08-11 00:00:00

  • Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase.

    abstract::Despite high structural homology between NO reductases (NORs) and heme-copper oxidases (HCOs), factors governing their reaction specificity remain to be understood. Using a myoglobin-based model of NOR (FeBMb) and tuning its heme redox potentials (E°') to cover the native NOR range, through manipulating hydrogen bondi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1720298115

    authors: Bhagi-Damodaran A,Reed JH,Zhu Q,Shi Y,Hosseinzadeh P,Sandoval BA,Harnden KA,Wang S,Sponholtz MR,Mirts EN,Dwaraknath S,Zhang Y,Moënne-Loccoz P,Lu Y

    更新日期:2018-06-12 00:00:00

  • Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin.

    abstract::The synaptic vesicle membrane protein synaptotagmin (tagmin) is essential for fast, calcium-dependent, neurotransmitter release and is likely to be the calcium sensor for exocytosis, because of its many calcium-dependent properties. Polyphosphoinositides are needed for exocytosis, but it has not been known why. We now...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.23.13327

    authors: Schiavo G,Gu QM,Prestwich GD,Söllner TH,Rothman JE

    更新日期:1996-11-12 00:00:00

  • Nonenzymatic sequence-specific cleavage of single-stranded DNA.

    abstract::Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-depend...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.4.963

    authors: Chu BC,Orgel LE

    更新日期:1985-02-01 00:00:00

  • Older mothers produce more successful daughters.

    abstract::Annual reproductive success and senescence patterns vary substantially among individuals in the wild. However, it is still seldom considered that senescence may not only affect an individual but also affect age-specific reproductive success in its offspring, generating transgenerational reproductive senescence. We use...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1908551117

    authors: Kroeger SB,Blumstein DT,Armitage KB,Reid JM,Martin JGA

    更新日期:2020-03-03 00:00:00

  • Avian reovirus mRNAs are nonfunctional in infected mouse cells: translational basis for virus host-range restriction.

    abstract::Avian reovirus S1133 penetrates and uncoats in suspension cultures of mouse L cells. The multiple species of viral transcripts are produced in the cytoplasm of the infected cell, but they fail to associate with polysomes, consistent with the absence of viral protein synthesis. The selective block in avian virus mRNA t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.85.12.4257

    authors: Benavente J,Shatkin AJ

    更新日期:1988-06-01 00:00:00

  • Light-activated protein interaction with high spatial subcellular confinement.

    abstract::Methods to acutely manipulate protein interactions at the subcellular level are powerful tools in cell biology. Several blue-light-dependent optical dimerization tools have been developed. In these systems one protein component of the dimer (the bait) is directed to a specific subcellular location, while the other com...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1713845115

    authors: Benedetti L,Barentine AES,Messa M,Wheeler H,Bewersdorf J,De Camilli P

    更新日期:2018-03-06 00:00:00

  • Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy.

    abstract::Dynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activation remains insufficiently explored, in large part because metals like copper and iron are typically studied as static cellular n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1009932108

    authors: Dodani SC,Domaille DW,Nam CI,Miller EW,Finney LA,Vogt S,Chang CJ

    更新日期:2011-04-12 00:00:00

  • Origin of the avian predentary and evidence of a unique form of cranial kinesis in Cretaceous ornithuromorphs.

    abstract::The avian predentary is a small skeletal structure located rostral to the paired dentaries found only in Mesozoic ornithuromorphs. The evolution and function of this enigmatic element is unknown. Skeletal tissues forming the predentary and the lower jaws in the basal ornithuromorph Yanornis martini are identified usin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1911820116

    authors: Bailleul AM,Li Z,O'Connor J,Zhou Z

    更新日期:2019-12-03 00:00:00

  • An alternative pathway for signal flow from rod photoreceptors to ganglion cells in mammalian retina.

    abstract::Rod signals in the mammalian retina are thought to reach ganglion cells over the circuit rod-->rod depolarizing bipolar cell-->AII amacrine cell-->cone bipolar cells-->ganglion cells. A possible alternative pathway involves gap junctions linking the rods and cones, the circuit being rod-->cone-->cone bipolar cells-->g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.23.10658

    authors: DeVries SH,Baylor DA

    更新日期:1995-11-07 00:00:00