138 research outputs found
Discovery of High-Affinity Protein Binding Ligands – Backwards
BACKGROUND: There is a pressing need for high-affinity protein binding ligands for all proteins in the human and other proteomes. Numerous groups are working to develop protein binding ligands but most approaches develop ligands using the same strategy in which a large library of structured ligands is screened against a protein target to identify a high-affinity ligand for the target. While this methodology generates high-affinity ligands for the target, it is generally an iterative process that can be difficult to adapt for the generation of ligands for large numbers of proteins. METHODOLOGY/PRINCIPAL FINDINGS: We have developed a class of peptide-based protein ligands, called synbodies, which allow this process to be run backwards--i.e. make a synbody and then screen it against a library of proteins to discover the target. By screening a synbody against an array of 8,000 human proteins, we can identify which protein in the library binds the synbody with high affinity. We used this method to develop a high-affinity synbody that specifically binds AKT1 with a K(d)<5 nM. It was found that the peptides that compose the synbody bind AKT1 with low micromolar affinity, implying that the affinity and specificity is a product of the bivalent interaction of the synbody with AKT1. We developed a synbody for another protein, ABL1 using the same method. CONCLUSIONS/SIGNIFICANCE: This method delivered a high-affinity ligand for a target protein in a single discovery step. This is in contrast to other techniques that require subsequent rounds of mutational improvement to yield nanomolar ligands. As this technique is easily scalable, we believe that it could be possible to develop ligands to all the proteins in any proteome using this approach
Observation of B(s)0→J/ψpp¯ decays and precision measurements of the B(s)0 masses
The first observation of the decays
B
0
(
s
)
→
J
/
ψ
p
¯
p
is reported, using proton-proton collision data corresponding to an integrated luminosity of
5.2
fb
−
1
, collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are
B
(
B
0
→
J
/
ψ
p
¯
p
)
=
[
4.51
±
0.40
(
stat
)
±
0.44
(
syst
)
]
×
10
−
7
,
B
(
B
0
s
→
J
/
ψ
p
¯
p
)
=
[
3.58
±
0.19
(
stat
)
±
0.39
(
syst
)
]
×
10
−
6
. For the
B
0
s
meson, the result is much higher than the expected value of
O
(
10
−
9
)
. The small available phase space in these decays also allows for the most precise single measurement of both the
B
0
mass as
5279.74
±
0.30
(
stat
)
±
0.10
(
syst
)
MeV
and the
B
0
s
mass as
5366.85
±
0.19
(
stat
)
±
0.13
(
syst
)
MeV
Measurement of D s <sup>±</sup> production asymmetry in pp collisions at √s=7 and 8 TeV
The inclusive production asymmetry is measured in collisions
collected by the LHCb experiment at centre-of-mass energies of
and 8 TeV. Promptly produced mesons are used, which decay as
, with . The measurement is
performed in bins of transverse momentum, , and rapidity, ,
covering the range GeV and . No kinematic
dependence is observed. Evidence of nonzero production asymmetry is
found with a significance of 3.3 standard deviations.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2018-010.htm
Observation of the decay Λ <sub>b</sub> <sup>0</sup> → ψ(2S)pπ<sup>−</sup>
International audienceThe Cabibbo-suppressed decay Λ → ψ(2S)pπ is observed for the first time using a data sample collected by the LHCb experiment in proton-proton collisions corresponding to 1.0, 2.0 and 1.9 fb of integrated luminosity at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The ψ(2S) mesons are reconstructed in the μμ final state. The branching fraction with respect to that of the Λ → ψ(2S)pK decay mode is measured to b
Search for CP violation in Λb0→pK− and Λb0→pπ− decays
A search for CP violation in Λb0→pK− and Λb0→pπ− decays is presented using a sample of pp collisions collected with the LHCb detector and corresponding to an integrated luminosity of 3.0fb−1. The CP -violating asymmetries are measured to be ACPpK−=−0.020±0.013±0.019 and ACPpπ−=−0.035±0.017±0.020, and their difference ACPpK−−ACPpπ−=0.014±0.022±0.010, where the first uncertainties are statistical and the second systematic. These are the most precise measurements of such asymmetries to date
Test of lepton universality in decays
The first simultaneous test of muon-electron universality using
and decays is performed, in two ranges of the dilepton
invariant-mass squared, . The analysis uses beauty mesons produced in
proton-proton collisions collected with the LHCb detector between 2011 and
2018, corresponding to an integrated luminosity of 9 . Each
of the four lepton universality measurements reported is either the first in
the given interval or supersedes previous LHCb measurements. The
results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb
public pages
Evidence for an nc(1S)ff- resonance in B0 yc(1S)K+ decays
A Dalitz plot analysis of B0→ηc(1S)K+π- decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s=7,8 and 13TeV , corresponding to a total integrated luminosity of 4.7fb-1 . A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S)π- resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096±20-22+18MeV and 152±58-35+60MeV , respectively. The spin-parity assignments JP=0+ and JP=1- are both consistent with the data. In addition, the first measurement of the B0→ηc(1S)K+π- branching fraction is performed and gives B(B0→ηc(1S)K+π-)=(5.73±0.24±0.13±0.66)×10-4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions
Observation of Two New Excited Ξb0 States Decaying to Λb0 K-π+
Two narrow resonant states are observed in the Λb0K-π+ mass spectrum using a data sample of proton-proton collisions at a center-of-mass energy of 13 TeV, collected by the LHCb experiment and corresponding to an integrated luminosity of 6 fb-1. The minimal quark content of the Λb0K-π+ system indicates that these are excited Ξb0 baryons. The masses of the Ξb(6327)0 and Ξb(6333)0 states are m[Ξb(6327)0]=6327.28-0.21+0.23±0.12±0.24 and m[Ξb(6333)0]=6332.69-0.18+0.17±0.03±0.22 MeV, respectively, with a mass splitting of Δm=5.41-0.27+0.26±0.12 MeV, where the uncertainties are statistical, systematic, and due to the Λb0 mass measurement. The measured natural widths of these states are consistent with zero, with upper limits of Γ[Ξb(6327)0]<2.20(2.56) and Γ[Ξb(6333)0]<1.60(1.92) MeV at a 90% (95%) credibility level. The significance of the two-peak hypothesis is larger than nine (five) Gaussian standard deviations compared to the no-peak (one-peak) hypothesis. The masses, widths, and resonant structure of the new states are in good agreement with the expectations for a doublet of 1D Ξb0 resonances
Observation of a resonant structure near the threshold in the decay
An amplitude analysis of the decay is carried out to
study for the first time its intermediate resonant contributions, using
proton-proton collision data collected with the LHCb detector at centre-of-mass
energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as
, is observed in the invariant-mass spectrum with
significance greater than 12 standard deviations. The mass, width and the
quantum numbers of the structure are measured to be MeV,
MeV and , respectively, where the first
uncertainties are statistical and the second systematic. The properties of the
new structure are consistent with recent theoretical predictions for a state
composed of quarks. Evidence for an additional structure is
found around 4140 MeV in the invariant mass, which might be
caused either by a new resonance with the assignment or by a coupled-channel effect.Comment: All figures and tables, along with any supplementary material and
additional information, are available at
https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb
public pages
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