Valine moneycontrol
The polypeptide may be capable of interacting with (e.g., specifically binding) P-glycoprotein. The invention also features a polypeptide including (a) an amino acid sequence having at least 50% (e.g., at least 60%, 70%, 80%, 90%, 95%, 99%, or 100%) identity to the sequence DGIWKASFTTFTVTKYWFYR (SEQ ID NO: 1) or VTKYWFYR (SEQ ID NO: 2), and (b) a heterologous sequence (e.g., any sequence described herein). The invention also features a composition including the polypeptide and a pharmaceutically acceptable carrier.
![valine moneycontrol valine moneycontrol](http://www.t3db.ca/structures/T3D4370/image.png)
In some embodiments, the polypeptide is soluble or the polypeptide is substantially pure. In other embodiments where the polypeptide has sequence identity to VTKYWFYR (SEQ ID NO: 2), the polypeptide has a valine or leucine at the position corresponding to the first amino acid, has a tyrosine at the position corresponding to the fourth amino acid, has a lysine or arginine at the position corresponding to the eighth amino acid, or any combination thereof. In certain embodiments, a polypeptide having sequence identity to DGIWKASFTTFTVTKYWFYR (SEQ ID NO: 1) has a valine or leucine at the position corresponding to the thirteenth amino acid, has a tyrosine at the position corresponding to the sixteenth amino acid, has a lysine or arginine at the position corresponding to the twentieth amino acid, or any combination thereof. In a first aspect, the invention features a polypeptide including an amino acid sequence having at least 50% (e.g., at least 60%, 70%, 80%, 90%, 95%, 99%, or 100%) identity to the sequence DGIWKASFTTFTVTKYWFYR (SEQ ID NO: 1) or VTKYWFYR (SEQ ID NO: 2) or a peptide described in Table 1, where the polypeptide is less than 170 (e.g., less than 150, 125, 100, 75, 50, 40, 30, 25, 20, 15) amino acids in length. Given the involvement of P-gp substrates in disease, there is a need to develop therapeutic approaches aimed at regulating P-gp function, which can reduce the accumulation of P-gp substrates, can inhibit cellular migration or angiogenesis, or can treat neurological disorders and other diseases. Apart from their efflux transport activity, P-glycoproteins are also known to play a role in cellular migration and angiogenesis. Indeed, neurological disorders including but not limited to epilepsy, Alzheimer's disease and Huntington's disease are associated with overexpression of ABC efflux transporters or substrates. P-glycoproteins have also been linked to neurological diseases. Indeed, P-gp interacts with a wide variety of anti-cancer drugs leading to a decrease in their intracellular concentrations ultimately leading to failure of chemotherapy. P-glycoprotein is associated with multi-drug resistance. Recent work suggests that two P-gp populations co-exist in the plasma membrane surrounded by different cholesterol concentration in the P-gp closed microenvironment (Barakat et al., Biochem. This particular localization seems to be important for P-gp ATPase and transport activities.
![valine moneycontrol valine moneycontrol](https://d2gdaxkudte5p.cloudfront.net/system/images/V42020-1000.0.jpg)
Caveolae may act as signaling platforms and can be identified by the presence of specific markers such as caveolin-1, -2, and -3. P-glycoprotein is localized at the plasma membrane, more specifically in microdomains enriched in cholesterol called caveolae. P-glycoprotein is an efflux pump protecting the structural and functional integrity of the organs and tissues on which it is expressed. P-glycoprotein (P-gp) is an ABC transporter, product of the MDR1 gene, found in the liver, gut, gonads, kidneys, biliary system, brain, and other organs. ABC transporters appear to have developed as a mechanism to protect the body from harmful substances. These transporters are involved in unidirectional substrate translocation and use ATP as the energy source to activate the extrusion process. This invention also relates to the treatment of diseases associated with cellular migration and/or angiogenesis and neurological diseases.ĪBC (ATP-Binding Cassette) transporters superfamily members are expressed on most mammalian tissues with excretory and/or barrier function. This invention also relates to the treatment of diseases resulting from accumulation of P-glycoprotein substrates. The invention relates to the field of therapeutic compounds, their uses, methods of use and compositions comprising them.