Posts

Showing posts with the label HAMLET

Note: Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex

Image
Note: Bladder cancer therapy using a conformationally fluid tumoricidal peptide complex Doi: 10.1038/s41467-021-23748-y Overall Define a peptide-based molecular approach for targeting and killing tumor cells Evidence of its clinical application ( NCT03560479 ) Peptide -- > 39 residue showed to gain lethality for killing tumor cells by forming oleic acid complexes (alpha1-oleate) Using NMR to study the structural complex of alpha1-oleate Lipid core is surrounded by alpha-helical peptide motif Clinical trial Non-muscle invasive bladder cancer Shred tumor cells contain alpha1-oleate -- no side effects Treated tumor -- demonstrate apoptosis Toxicity comes from the folding status Formation of amorphous aggregates and amyloid fibrils Antimicrobial peptide the ability to destabilize lipid bilayers has been proposed to reside in the three dimensional conformation rather than the amino acid sequence Function of alpha-lactalbumin In its native state, the protein serves as a substrate specifie...

Note: Conversion of alpha-lactalbumin to a protein inducing apoptosis

Note: Conversion of alpha-lactalbumin to a protein inducing apoptosis Doi: 10.1073/pnas.97.8.4221 Conversion to HAMLET (human a-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor. Identified the folding change and the fatty acid as two key elements that define HAMLET It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate. The state of protein folding can determine the cellular function. The factor determines the folding; Amino acid sequence Thermodynamics force Kinetic of protein folding Higher-energy barriers between different conformations -- overcoming by chaperones Also have other systems which relieve the thermodynamics barrier Partially unfolded is stabilized by cofactor which is the fatty acid - to be specific oleic acid This paper can identify the cofactor (lipid - C18)  con...