tube ubiquitin, Tandem Ubiquitin Binding Entities (TUBEs) as Tools to Explore Ubiquitin-Proteasome System and PROTAC Drug Discovery

Tandem Ubiquitin Binding Entities (TUBEs) as Tools to Explore Ubiquitin-Proteasome System and PROTAC Drug Discovery

The ubiquitin proteasome system (UPS) is a fancy pathway that entails a number of enzymes and culminates within the formation of a polyubiquitin chain on a goal protein. As its significance is turning into extra evident in drug discovery, there’s a renewed curiosity in understanding the function that polyubiquitin chains play.
This has been a problem, largely because of the lack of experimental instruments for detecting the polyubiquitinated types of a protein of curiosity (POI). Tandem Ubiquitin Binding Entities (TUBEs) are engineered protein domains that bind particularly to polyubiquitin chains. These polyubiquitin affinity matrices are extremely delicate as they bind to polyubiquitin chains within the nanomolar vary.
They exist in two kinds: pan-selective TUBEs and chain-selective TUBEs. The flexibility of TUBEs to be conjugated to totally different entities is really what makes them distinctive. TUBEs are utilized in all kinds of experiments comparable to in protein pulldowns to complement for polyubiquitinated proteins. They’re an alternative choice to ubiquitin antibodies in Western blots.
Additional, TUBEs are used as seize reagents for immobilizing polyubiquitinated proteins on a microtiter plate. Using TUBEs as parts of in vitro and cell-based assays presents the distinctive function of confirming and assessing the polyubiquitination of a POI in response to inhibitors, activators, or PROTAC® molecules. Subsequently, TUBEs not solely play a giant function in finding out the usbut even have an enormous potential for rushing up the drug discovery course of.

A Novel Luminescence-Primarily based Excessive-Throughput Method for Mobile Decision of Protein Ubiquitination Utilizing Tandem Ubiquitin Binding Entities (TUBEs).

Protein turnover is extremely regulated by the posttranslational strategy of ubiquitination. Deregulation of the ubiquitin proteasome system (UPS) has been implicated in most cancers and neurodegenerative illnesses, and modulating this method has confirmed to be a viable strategy for therapeutic intervention. The event of novel applied sciences that allow high-throughput research of substrate protein ubiquitination is essential for UPS drug discovery.
Typical approaches for finding out ubiquitination both have excessive protein necessities or depend on exogenous or modified ubiquitin moieties, thus limiting their utility. As a way to circumvent these points, we developed a high-throughput live-cell assay that mixes the NanoBiT luminescence-based expertise with tandem ubiquitin binding entities (TUBEs) to resolve substrate ubiquitination.
To reveal the effectiveness and utility of this assay, we studied compound-induced ubiquitination of the G to S Part Transition 1 (GSPT1) protein. Utilizing this assay, we characterised compounds with various ranges of GSPT1 ubiquitination exercise.
This methodology gives a live-cell-based strategy for assaying substrate ubiquitination that may be tailored to review the kinetics of ubiquitin switch onto a substrate protein of curiosity. As well as, our outcomes present that this strategy is transportable for finding out the ubiquitination of goal proteins with various features.

New insights into host-parasite ubiquitin proteome dynamics in P. falciparum contaminated purple blood cells utilizing a TUBEs-MS strategy.

Malaria, attributable to Plasmodium falciparum (P. falciparum), ranks as some of the baleful infectious illnesses worldwide. New antimalarial therapies are wanted to face present or rising drug resistant strains. Protein degradation seems to play a big function through the asexual intraerythrocytic developmental cycle (IDC) of P. falciparum.
Inhibition of the ubiquitin proteasome system (UPS), a serious intracellular proteolytic pathway, successfully reduces an infection and parasite replication. P. falciparum and erythrocyte UPS coexist throughout IDC however the nature of their relationship is essentially unknown. We used an strategy primarily based on Tandem Ubiquitin-Binding Entities (TUBEs) and 1D gel electrophoresis adopted by mass spectrometry to determine main parts of the TUBEs-associated ubiquitin proteome of each host and parasite throughout ring, trophozoite and schizont levels.
Ring-exported protein (REX1), a P. falciparum protein situated in Maurer’s clefts and vital for parasite nutrient import, was discovered to succeed in a most stage of ubiquitylation in trophozoites stage. The Homo sapiens (H. sapiens) TUBEs related ubiquitin proteome decreased through the an infection, whereas the equal P. falciparum TUBEs-associated ubiquitin proteome counterpart elevated. Main mobile processes comparable to DNA restore, replication, stress response, vesicular transport and catabolic occasions look like regulated by ubiquitylation alongside the IDC P. falciparum an infection.

The Hectd1 ubiquitin ligase is required for growth of the top mesenchyme and neural tube closure.

Closure of the cranial neural tube is determined by regular growth of the top mesenchyme. Homozygous-mutant embryos for the ENU-induced open thoughts (opm) mutation exhibit exencephaly related to defects in head mesenchyme growth and dorsal-lateral hinge level formation. The top mesenchyme in opm mutant embryos is denser than in wildtype embryos and shows an irregular mobile group.
Since cells that originate from each the cephalic paraxial mesoderm and the neural crest populate the top mesenchyme, we explored the origin of the irregular head mesenchyme. opm mutant embryos present apparently regular growth of neural crest-derived constructions. Moreover, the irregular head mesenchyme in opm mutant embryos will not be derived from the neural crest, however as an alternative expresses molecular markers of cephalic mesoderm.
We additionally report the identification of the opm mutation within the ubiquitously expressed Hectd1 E3 ubiquitin ligase. Two totally different Hectd1 alleles trigger incompletely penetrant neural tube defects in heterozygous animals, indicating that Hectd1 perform is required at a important threshold for neural tube closure. This low penetrance of neural tube defects in embryos heterozygous for Hectd1 mutations means that Hectd1 needs to be thought-about as candidate susceptibility gene in human neural tube defects.
tube ubiquitin, Tandem Ubiquitin Binding Entities (TUBEs) as Tools to Explore Ubiquitin-Proteasome System and PROTAC Drug Discovery

A quick stream tube examine of fuel section H/D trade of multiply protonated ubiquitin.

An electrospray ionization (ESI)/fast-flow method has been utilized to the examine of fuel section hydrogen/deuterium (H/D) trade kinetics. Multiply charged ubiquitin ions [ubiquitin + nH](n)(+), in cost states n = 7-13, have been reacted with ND(3). The conduct of ND(3) as trade reagent is totally different from that of the beforehand studied reagents, D(2)O and CH(3)OD.
Opposite to these, the utmost variety of exchanged hydrogen atoms and the general trade fee have been noticed to extend with rising cost state of the ubiquitin ions. The outcomes are reagent-dependent as a result of the trade mechanisms are totally different for the totally different reagents. This remark is in settlement with a current conclusion by Beauchamp and colleagues that opposite to the idea usually expressed in earlier research, H/D trade kinetics could indirectly replicate ion constructions.
The outcomes for all three reagents are, nonetheless, according to observations of earlier ion mobility experiments that with rising cost state the conformers change from extra compact, partially folded constructions to elongated practically linear ones. H/D trade of (ubiquitin + 13H)(13+) with ND(3) results in two separated ion populations reflecting the potential existence of two conformers with totally different trade charges. The ions (ubiquitin + 8H)(8+) and (ubiquitin + 11H)(11+) signify {a partially} folded construction and an unfolded construction, respectively, and have been studied in better element.
The relative abundances of ions have been measured in steps of 0.5 m/z (mass-to-charge ratio), as a perform of the ND(3) stream fee. The experimental outcomes have been simulated by laptop fitted curves primarily based on a not too long ago developed algorithm. The algorithm permits the extraction of units of grouped fee constants. Eight fee fixed teams have been deduced for every of the 2 ions.

Tube Rack

BV1010-1520 1 PC
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BV1010-25 1 PC
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Drain tube

2393092 8unit
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Tube holder

R2020-0507 1 PC
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R2020-150 1 PC
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Tube holder

R2020-1520 1 PC
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Tube holder

R2020-500 1 PC
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Tube holder

R2020-PCR 1 PC
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Absorption Tube

QAD3 EACH
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Filter Tube

TUB2812 PK10
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ubiquitin (Ubiquitin) Antibody

abx022608-02ml 0.2 ml
EUR 610.8

ubiquitin (Ubiquitin) Antibody

20-abx013245
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  • EUR 477.60
  • EUR 594.00
  • 100 ug
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  • 300 µg

ubiquitin (ubiquitin) Antibody

abx037750-100ug 100 ug
EUR 469.2

ubiquitin (Ubiquitin) Antibody

20-abx444887
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ubiquitin (Ubiquitin) Antibody

20-abx444896
  • EUR 627.60
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ubiquitin (Ubiquitin) Antibody

abx444934-100ug 100 ug
EUR 427.2

ubiquitin (Ubiquitin) Antibody

20-abx445164
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  • 200 ul
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ubiquitin (ubiquitin) Antibody

abx239197-100ug 100 ug
EUR 610.8

mini capillary tubes 1 mm pk/100

EVS1100-TUBE-1.0 ea
EUR 78

mini capillary tubes 1.5 mm pk/100

EVS1100-TUBE-1.5 ea
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maxi capillary tubes 1 mm pk/100

EVS1300-TUBE-1.0 ea
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FlexiFuge Tube Rotor for .2mL PCR Tube Strips

ARG1122 EACH
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ubiquitin (Ubiquitin) Antibody (Biotin)

abx442853-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (Biotin)

abx442862-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (FITC)

abx443133-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (FITC)

abx443142-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (HRP)

abx443413-200ug 200 ug
EUR 727.2

ubiquitin (Ubiquitin) Antibody (HRP)

abx443422-200ug 200 ug
EUR 727.2

ubiquitin (Ubiquitin) Antibody (PerCP)

abx443975-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (PerCP)

abx443984-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (RPE)

abx444256-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (RPE)

abx444265-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (Streptavidin)

abx444537-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (Streptavidin)

abx444546-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ALP)

abx444810-100ug 100 ug
EUR 477.6

ubiquitin (Ubiquitin) Antibody (APC)

abx444814-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (Biotin)

abx444818-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (FITC)

abx444822-100ug 100 ug
EUR 477.6

ubiquitin (Ubiquitin) Antibody (HRP)

abx444826-100ug 100 ug
EUR 477.6

ubiquitin (Ubiquitin) Antibody (PerCP)

abx444834-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (RPE)

abx444838-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (Streptavidin)

abx444842-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ALP)

abx447954-200ul 200 ul
EUR 744

ubiquitin (Ubiquitin) Antibody (APC)

abx447955-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (Biotin)

abx447956-200ul 200 ul
EUR 744

ubiquitin (Ubiquitin) Antibody (FITC)

abx447957-200ul 200 ul
EUR 744

ubiquitin (Ubiquitin) Antibody (HRP)

abx447958-200ul 200 ul
EUR 727.2

ubiquitin (Ubiquitin) Antibody (PerCP)

abx447960-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (RPE)

abx447961-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (Streptavidin)

abx447962-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ALP)

abx442291-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (ALP)

abx442300-200ug 200 ug
EUR 744

ubiquitin (Ubiquitin) Antibody (APC)

abx442572-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (APC)

abx442581-200ug 200 ug
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Sterile Centrifuge Tube

C1005-T5-ST 1 PC
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5ml Tube holder

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Digital Tube Roller

abx725018-1Unitwith10Rollers 1 Unit with 10 Rollers
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Tube Tags 38x6.5mm

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Lamp Fluorescent Tube

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Tube support 1.5mL

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Rubber tube replacement

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Direct Tube Marker

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Paxgene Tube Kit

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TES1100 PK250
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TES1106 PK250
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Ubiquitin

A20038 2 ml
EUR 94.8

Ubiquitin

A00038 6 ml
EUR 129.6

Ubiquitin

A00038.0025 25 ml
EUR 261.6

Ubiquitin

MO18001 100 ul
EUR 579.6

Ubiquitin

MO22152 100 ul
EUR 522

Ubiquitin

PR27083 50 ug
EUR 381.6

ubiquitin (Ubiquitin) Antibody (ATTO 390)

abx440043-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 390)

abx440052-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 390)

abx444778-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 488)

abx444782-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 565)

abx444786-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 594)

abx444790-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 633)

abx444794-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 655)

abx444798-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 680)

abx444802-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 700)

abx444806-100ug 100 ug
EUR 493.2

ubiquitin (Ubiquitin) Antibody (ATTO 390)

abx447946-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 488)

abx447947-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 565)

abx447948-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 594)

abx447949-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 633)

abx447950-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 655)

abx447951-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 680)

abx447952-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 700)

abx447953-200ul 200 ul
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 488)

abx440324-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 488)

abx440333-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 565)

abx440605-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 565)

abx440614-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 594)

abx440886-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 594)

abx440895-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 633)

abx441167-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 633)

abx441176-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 655)

abx441448-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 655)

abx441457-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 680)

abx441729-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 680)

abx441738-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 700)

abx442010-200ug 200 ug
EUR 760.8

ubiquitin (Ubiquitin) Antibody (ATTO 700)

abx442019-200ug 200 ug
EUR 760.8

Test Tube Rack Holder (for 50 Ml Test Tube Racks)

480169 EACH
EUR 53.35

Fallopian tube disease spectrum (fallopian tube cancer progression) tissue array

UTE601 each
EUR 306
Description: Fallopian tube disease spectrum (fallopian tube cancer progression) tissue array, including pathology grade, TNM and clinical stage, 30 cases/60 cores

mini tube gel insert

EVS1100-TUBEINSERT ea
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maxi tube gel insert

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PIPET CONTROLLER SILICONE TUBE

357483 1/pk
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Description: Falcon Liquid Handling Equipment; Falcon Pipet Controllers and Accessories

Tubulin Epsilon (TUBe) Antibody

20-abx101415
  • EUR 526.80
  • EUR 159.60
  • EUR 1479.60
  • EUR 710.40
  • EUR 393.60
  • 100 ug
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  • 1 mg
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Tubulin Epsilon (TUBe) Antibody

20-abx128096
  • EUR 510.00
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  • EUR 1446.00
  • EUR 693.60
  • EUR 393.60
  • 100 ug
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Tube Holder Set (Small

MSS-1100 mL
EUR 176.4
Description: Please reffer to the technical data sheet for more detail information for this item. Our dedicated team would be happy to assist you via live chat, email or phone.

Recombinant Tubulin Epsilon (TUBe)

4-RPE719Hu01
  • EUR 582.34
  • EUR 279.60
  • EUR 1853.76
  • EUR 697.92
  • EUR 1275.84
  • EUR 465.60
  • EUR 4454.40
  • 100 ug
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  • 1 mg
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Description: Recombinant Human Tubulin Epsilon expressed in: E.coli

Recombinant Tubulin Epsilon (TUBe)

4-RPE719Mu01
  • EUR 603.84
  • EUR 285.60
  • EUR 1934.40
  • EUR 724.80
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  • EUR 480.00
  • EUR 4656.00
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Description: Recombinant Mouse Tubulin Epsilon expressed in: E.coli

Microcentrifuge Tube 1.5mL (Axygen)

TUBE1.5AX-S 500box
EUR 255.6
Description: Screw-cap tubes, 1.5 mL, Axygen brand, with caps for use in microcentrifuge style Bullet Blenders with a "W" in the serial number. Sterile, RNase & DNase free.

wl tube 6 w

VLT6-WL ea
EUR 87.6

wl tube 8 w

VLT8-WL ea
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Tube Tags 12.5x24mm Medium

LAB1230 PK1000
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Multi-use Milling Tube

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Trayster Tube Insert TR1

MIX1042 EACH
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MIX5120 PK4
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OVE3011 EACH
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OVE3012 EACH
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Techne 15ml Tube Holder

OVE3019 EACH
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OVE3021 EACH
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Techne Tube Large FHB16

OVE3022 EACH
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OVE3024 EACH
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OVE3026 PK4
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Microcapillary tube Drummond Microcaps

P1924-1PAK PK100
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Tube rack round floating

R7901-5EA PK5
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Tube Rack EPS 100x1.5ml

RAC0410 PK10
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Melting Point Tube 75x1.35mm

HAE3151 PK1000
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HAE3152 PK1000
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Cristaseal Capillary Tube Sealant

HAE3160 PK10
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Bridge for 15ml tube

HOM2650 EACH
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HOM2654 EACH
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E5353040148 EACH
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Oil Centrifuge Tube 100ml

F87990 PK2
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LowProfile 5ml2D WhitePatch Tube

SAM0200 PK240
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SAM0204 PK240
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IKA Test Tube Attachment

SHA2002 EACH
EUR 560.88

Tube Marker Ribbon White

PCR1416 EACH
EUR 136.8
These fee constants correspond to 32 and 44 H/D exchanges for the 8+ and 11+ charged ions, respectively. The outcomes point out increased particular person charges for many of the exchanged atoms within the 11+ ion in comparison with the 8+ ion.

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