| abstract |
Provided herein is a stabilized αCT polypeptide comprising an α-helical segment, wherein the polypeptide is of formula (I-1) or formula (I-2) R f - [X AA] s -X A1 -X A2 -X A3 -X A4 -X A5 -X A6 -X A7 -X A8 -X A9 -X A10 -X A11 -X A12 -X A13 -X A14 - [X AA] t -R e (I-1) R f - [X AA] s -X C1 -X C2 -X C3 -X C4 -X C5 -X C6 -X C7 -X C8 -X C9 -X C10 -X C11 -X C12 -X C13 -X C14 -X C15 -X C16 -X C17 -X C18 -X C19 -X C20- [X AA ] t -R e (I-2) It is. The αCT polypeptide binds to the insulin receptor, and the αCT polypeptide includes at least one staple (ie, two cross-linked amino acids) and / or at least one stitch (ie, three cross-linked amino acids). Further provided are insulin analogs comprising stapled or stitched αCT polypeptides, pharmaceutical compositions thereof, methods of use, eg, methods of treating diabetic conditions or complications thereof. |