Sandbox Ben Whiteside: Difference between revisions
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[https://en.wikipedia.org/wiki/Pramlintide Pramlintide] is a synthetic analog of amylin that is commonly used in accordance with mealtime [https://en.wikipedia.org/wiki/Insulin insulin] to help treat type 1 and 2 diabetic patients. This drug binds to AMYR competitively, increasing the AMYR GPCR signaling. Increased action of the AMYR receptor has been shown to modestly lower HbA1c levels, which is often accompanied by weight loss (cite 5). Pramlintide binds with more affinity than amylin due to mutations from hydrophobic residues A29, S28, S29, and S37 to proline. The proline residues increase the rigidity of the ligand by creating unfavorable phi and psi angles, which improves the ability of the ligand to bind AMYR. Pramlintide treatment has also been shown to consistently reduce [https://en.wikipedia.org/wiki/Amyloid_plaques Amyloid β plaque] aggregation in rodent models with [https://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] (Gingell et al. 2014). | [https://en.wikipedia.org/wiki/Pramlintide Pramlintide] is a synthetic analog of amylin that is commonly used in accordance with mealtime [https://en.wikipedia.org/wiki/Insulin insulin] to help treat type 1 and 2 diabetic patients. This drug binds to AMYR competitively, increasing the AMYR GPCR signaling. Increased action of the AMYR receptor has been shown to modestly lower HbA1c levels, which is often accompanied by weight loss (cite 5). Pramlintide binds with more affinity than amylin due to mutations from hydrophobic residues A29, S28, S29, and S37 to proline. The proline residues increase the rigidity of the ligand by creating unfavorable phi and psi angles, which improves the ability of the ligand to bind AMYR. Pramlintide treatment has also been shown to consistently reduce [https://en.wikipedia.org/wiki/Amyloid_plaques Amyloid β plaque] aggregation in rodent models with [https://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] (Gingell et al. 2014). | ||
It has been thought that [https://en.wikipedia.org/wiki/Missense_mutation missense mutations] | It has been thought that [https://en.wikipedia.org/wiki/Missense_mutation missense mutations] in residues C2 and C7 of the amylin peptide could lead to an increased risk of Alzheimer's Disease (CITE). Because of the rigidity these cysteine resides provide, reductions of their disulfide interaction leads to an increased risk of amyloid plaques due to amylin misfolding and forming aggregates. During drug design, pharmaceutical companies have focused on maintaining amylin residues C2 and C7, as well as K1, which forms a acts as a hydrogen bond donor for the <scene name='10/1038828/N_term_disulfidenew/1'>E294 Side Chain</scene> and main chain carbonyl. Additionally, pharmaceuticals companies have also opted to maintain residues <scene name='10/1038819/Amidated_c_term/9'>Y37 and T36</scene>, which are critical residues in stabilizing the C terminus of amylin to the receptor binding site. While there are hardly differences in the helical portion of amylin and the syntehtic analgoue pramlintide, there is a difference in the extended random coil at the C terminus. | ||
[[Image:align.png|300px|left|thumb|Figure 3:Amylin (green) aligned with Pramlintide (red)]] | [[Image:align.png|300px|left|thumb|Figure 3:Amylin (green) aligned with Pramlintide (red)]] | ||
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== Student Contributors == | == Student Contributors == | ||
Andrew Helmerich,Mathias Vander Eide, Ben Whiteside | Andrew Helmerich, Mathias Vander Eide, Ben Whiteside | ||
