The N-terminal 17-residue stretch of huntingtin (htt^N17) folds into an amphipathic α-helix. The htt^N17–harboring polyQ peptides form oligomers that are mediated via the assembly of the htt^N17 α-helices. The oligomerization results in higher local concentration of the polyglutamine (polyQ) region, thereby facilitating amyloid formation. The htt^N17 co-assembles with the htt^N17-harbouring polyQ peptides, thereby reducing the local polyQ concentration, and consequently inhibiting aggregation. This study presents the aggregation inhibition of the exon I region of pathogenic huntingtin by htt^N17 and its analogs. The C-terminal amidation of htt^N17 is found to be essential for activity. The htt^N17 peptides with free amino terminus and the acetylated amino terminus possess comparable activity. The htt^N17 analog, wherein the Leu7 and Ala10 are substituted with 2-aminoisobutyric acid residues, exhibits significantly higher activity than the native htt^N17.

亨廷顿蛋白 (htt ^N17 )的 N 端 17 个残基折叠成两亲性 α-螺旋。htt ^N17- harboring polyQ 肽形成寡聚体，通过 htt ^N17 α-螺旋的组装介导。低聚导致聚谷氨酰胺 (polyQ) 区域的局部浓度更高，从而促进淀粉样蛋白的形成。htt ^N17与含有 htt ^{N17 的}polyQ 肽共同组装，从而降低局部 polyQ 浓度，从而抑制聚集。本研究介绍了 htt ^N17及其类似物对致病性亨廷顿蛋白外显子 I 区域的聚集抑制。htt ^N17的 C 端酰胺化被发现是活动必不可少的。具有游离氨基末端和乙酰化氨基末端的 htt ^N17肽具有相当的活性。htt ^N17类似物，其中 Leu7 和 Ala10 被 2-氨基异丁酸残基取代，表现出比天然 htt ^N17显着更高的活性。