Structure–activity relationships of globomycin analogues as antibiotics

Kiho, Toshihiro; Nakayama, Mizuka; Yasuda, Kayo; Miyakoshi, Shunichi; Inukai, Masatoshi; Kogen, Hiroshi

doi:10.1016/j.bmc.2003.10.055

Cited by 50 publications

(32 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…95 Structure activity relationship studies demonstrated that the hydroxyl of the Ser residue was critical for antibacterial activity. 96 The crystal structure of globomycin in complex with LspA, a SP-II from P. aeruginosa, 97 demonstrates that this Ser is in contact with the proposed catalytic Asp124 and Asp143 of the active site, and that the antibiotic occupies the substrate signal peptide-binding site. This structure should help to guide additional improvements to globomycin, to increase efficacy.…”

Section: Bacterial Proteases Untapped Antimicrobial Drug Targetsmentioning

confidence: 99%

Bacterial proteases, untapped antimicrobial drug targets

2016

View full text Add to dashboard Cite

Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs). Caseinolytic protease (ClpP) belongs to the AAA+ family of proteases, a group of multimeric barrel-shaped complexes whose activity is tightly regulated by associated AAA+ ATPases. The opportunity for chemical perturbation of these complexes is demonstrated by compounds targeting ClpP for inhibition, activation or perturbation of its associated ATPase. Meanwhile, SPs are also a proven antibiotic target. Responsible for the cleavage of targeting peptides during protein secretion, both type I and type II SPs have been successfully targeted by chemical inhibitors. As the threat of pan-antibiotic resistance continues to grow, these and other bacterial proteases offer an arsenal of novel antibiotic targets ripe for development.

show abstract

Section: Bacterial Proteases Untapped Antimicrobial Drug Targetsmentioning

confidence: 99%

Bacterial proteases, untapped antimicrobial drug targets

2016

View full text Add to dashboard Cite

show abstract

“…[29][30][31] FT-IR spectra of 31 were collected on a JASCO FT/IR-4200, using a NaCl liquid cell (0.1 mm path length) with toluene d-8. SEM, 3D scanning laser microscopy, and digital optical microscopy were performed using a VE-9800 SEM, a VK-9700 Generation II Color Laser Scanning Microscope, and a VHX-1000 (KEYENCE) digital optical microscope, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…28) Twentyseven tripeptides, 1-27, based on various combinations of Gly, Ala, and Val, were synthesized by repeated condensation and deprotection in the liquid phase (Chart 1). [29][30][31] Each amino acid benzyl ester (third fragment) was reacted with a Boc-protected amino acid (second fragment) under 1-hydroxybenzotriazole hydrate (HOBt · H 2 O)/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC · HCl)/triethylamine conditions in 27% to quantitative yields. The dipeptide was subsequently deprotected by removal of the Boc group in HCl/dioxane to give an O-benzyl dipeptide.…”

mentioning

confidence: 99%

Development of Supramolecular Organo-Gel Based on Tripeptide Skeletons

Azuma

Kuramochi

Tsubaki

2010

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

Low molecular weight (supramolecular) gels have attracted attention in the fields of supramolecular chemistry and material chemistry over the past two decades. [1][2][3][4][5][6] The gel phase is a wettable viscoelastic physical state that shares some properties of both liquid and solid phases. Gelation occurs when self-organizing gelators produce an entangled three-dimensional network of fibers that constrains the mobility of the embedded solvent molecules. Low molecular weight gelators based on amino acids, 7-10) ureas, [11][12][13] amides, [14][15][16] and saccharides [17][18][19] have been developed, and the responses of these gels to photo irradiation, 20,21) ultrasonic frequencies, 22,23) and biologically active agents 10,24,25) have been described. However, organic reactions (covalent bond forming reactions) in the gel phase have received relatively little attention. 26,27) We are trying to develop novel organic reactions in a supramolecular gel phase using a dualfunctional molecule that is capable of catalyzing reaction as well as forming gel. In this paper, we describe the synthesis and gelation properties of several tripeptide derivatives, which form the backbone of the dual-functional molecule.N-t-Butoxycarbonyl (Boc) and O-benzyl protected tripeptide gelators, composed of Gly, Ala, and Val, were designed because this combination was previously and accidentally shown to yield interesting gelation properties.28) Twentyseven tripeptides, 1-27, based on various combinations of Gly, Ala, and Val, were synthesized by repeated condensation and deprotection in the liquid phase (Chart 1). [29][30][31] Each amino acid benzyl ester (third fragment) was reacted with a Boc-protected amino acid (second fragment) under 1-hydroxybenzotriazole hydrate (HOBt · H 2 O)/1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC · HCl)/triethylamine conditions in 27% to quantitative yields. The dipeptide was subsequently deprotected by removal of the Boc group in HCl/dioxane to give an O-benzyl dipeptide. A Boc-protected amino acid (first fragment) was then introduced to the dipeptide under similar conditions to afford the desired tripeptides 1-27 in yields of 15-99%.The gelation abilities of the 27 tripeptide derivatives in each of ten organic solvents (hexane, EtOAc, CHCl 3 , CH 2 Cl 2 , acetone, acetonitrile, EtOH, MeOH, toluene, and chlorobenzene) were surveyed as follows. Each tripeptide/ solvent combination was mixed in a microtube and (as appropriate) irradiated with ultrasound for 30 min at temperatures ranging from room temperature to 60°C to afford a homogeneous solution. The solutions were stored in an incubator at 20°C for 24 h. When the tube was inverted and tapped, the absence of a fluid phase was defined as a gel (transparent or opaque gel), and a crumpled jelly object was defined as a partial gel. Table 1 shows the results of the first screening and the minimum gelation concentration for those tripeptide/solvent combinations that yielded a gel.The results shown in Table 1 indicate that toluene and ...

show abstract

“…Zurückgreifend auf die Synthese des bekannten Peptidthiazols 44 (Kapitel 1.5.3), wurde [201] (140) zunächst mit dem Azidothiol 50 umgesetzt und der Thioester 141 mit einer guten Ausbeute von 78% erhalten (Schema 3.14). Anschließende Aza-WittigCyclisierung und Thiazolinoxidation lieferte das Thiazol 142 mit einer Ausbeute von 84% über zwei Stufen.…”

Section: Synthese Der Peptidthiazoleunclassified

“…[36] Tristhiazolylpyridin 42, [37] (57), [36] 1,2-(Z)-Methoxycarbonyl-1,3-bis(trimethyl-silyloxy)-1,3-butadien (65), [37] 2-Nitro-6-(2'-tetrahydropyranyloxymethyl)phenyl-brenztrauben-säureethylester (75), [153] 3-Hydrox-ypyridin-5,6-bis(trideutero-methoxycarbonyl)-2-carbon-säuremethylester (97-d 6 ), [241] 131 3-Hydroxypicolinsäuremethylester (100), [278] L-Boc-Thr(TBS)-OH (140), [201] L-FmocThr(TBS)-OH (143), [202] 2'-Bromacetyl-pyridin (161), [219] 6-Brom-3-hydroxypicolinsäure-methyl-ester (204), [267] 4-(Tributyl-stannyl)-1-trityl-1H-imidazol (217), [269] 4,6-Dibrom-3-hydroxy-picolinsäure-diemethylester (228), [278] Dess-Martin-Periodinan, [312] 3-Hydroxypyridin-2,5,6-tricarbonsäure-trimethylester, [37] 3-Meth-oxypicolinsäuremethyl-ester(240) [308] Indol-2-boron-säurepinakolester, [313] Indol-3-boronsäurepinakol-ester, [314] 1H-Pyrrol-3-boronsäure-pinakolester, [315] 1-(Tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-boronsäurepinakol-ester, [268] Pyrazol-4-boronsäurepinakolester, [314] (R)-2-Azido-3-(tritylthio)-propansäureallyl-ester, [37] PyDOP. [225] Dichlormethan [316] die Sporen wurden anschließend geerntet und in Glycerol gelagert.…”

Section: Synthese Der Nicht Fluorierten Biscarboxamid-ligandenunclassified

Totalsynthese von Nosiheptid

Wojtas

Riedrich

et al. 2016

Angewandte Chemie

View full text Add to dashboard Cite

Eine Totalsynthese des bismakrocyclischen Thiopeptidantibiotikums Nosiheptid gelang durch den Aufbau einer voll funktionalisierten linearen Vorstufe und konsekutive Makrocyclisierungen. Schlüsselmerkmale waren eine kritische Makrothiolactonisierung und eine milde Entschützungsstrategie für den 3‐Hydroxypyridin‐Kern. Der Naturstoff war mit isoliertem authentischem Material im Hinblick auf spektroskopische Daten und antimikrobielle Aktivität identisch.

show abstract

Structure–activity relationships of globomycin analogues as antibiotics

Cited by 50 publications

References 30 publications

Bacterial proteases, untapped antimicrobial drug targets

Bacterial proteases, untapped antimicrobial drug targets

Development of Supramolecular Organo-Gel Based on Tripeptide Skeletons

Totalsynthese von Nosiheptid

Contact Info

Product

Resources

About