Good news! Cancer is history (soon)!
"Meet MYC, the shapeless protein responsible for making the majority of human cancer cases worse. UC Riverside researchers have found a way to rein it in, offering hope for a new era of treatments.
In healthy cells, MYC helps guide the process of transcription, in which genetic information is converted from DNA into RNA and, eventually, into proteins. “Normally, MYC’s activity is strictly controlled. In cancer cells, it becomes hyper active, and is not regulated properly,” ...
“MYC is less like food for cancer cells and more like a steroid that promotes cancer’s rapid growth,” ... “That is why MYC is a culprit in 75% of all human cancer cases.” ...
However, finding a way to control MYC was challenging because unlike most other proteins, MYC has no structure. “It’s basically a glob of randomness,” ... “Conventional drug discovery pipelines rely on well-defined structures, and this does not exist for MYC.” ...
describes a peptide compound that binds to MYC and suppresses its activity. ...
In the paper, the team describes a new peptide that binds directly to MYC with what is called sub-micro-molar affinity, which is getting closer to the strength of an antibody. In other words, it is a very strong and specific interaction. ..."
From the abstract:
"Here, we present the second generation of our bicyclic peptide library (NTB), featuring a stereodiversified structure and a simplified construction strategy. We utilized a tandem ring-opening metathesis and ring-closing metathesis reaction (ROM-RCM) to cyclize the linear peptide library in a single step, representing the first reported instance of this reaction being applied to the preparation of macrocyclic peptides. Moreover, the resulting bicyclic peptide can be easily linearized for MS/MS sequencing with a one-step deallylation process. We employed this library to screen against the E363-R378 epitope of MYC and identified several MYC-targeting bicyclic peptides. Subsequent in vitro cell studies demonstrated that one candidate, NT-B2R, effectively suppressed MYC transcription activities and cell proliferation."
Scientists tame chaotic protein fueling 75% of cancers (UC Riverside) Discovery opens window to more effective treatment
Figure 1. (A) Macrocyclization and linearization of the bicyclic peptide through ROM-RCM and deallylation reactions. In the cartoon illustration, the balls represent amino acid residues, and other solid shapes depict the functional groups that participate in the reaction. Green numbers and the green dashed bond illustrate regioisomerism. (B) Stereodiversity of 5-norbornene-2-carboxylic acid amide derivatives before and after cyclization. The eight isomers exhibit distinct stereo structures when combined with all l-amino acids. (C) Proline scanning results. The numbers indicate the positions of proline insertion in the linear precursor. The reaction yield was semiquantitatively determined by mass spectrometry. (D) Structures of the model peptide (FIVAL) regioisomers. (E) Conformation clusters of each isomer illustrated by different colors. Endo and exo refer to the stereostructure of the norbornene building block. The percent population of each conformation cluster is shown in the pie charts with corresponding colors.
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