Peptide Inhibitors of a-Amylase Based on Tendamistat: Development of Analogues with ϖ-Amino Acids Linking Critical Binding Segments

Title: Peptide Inhibitors of a-Amylase Based on Tendamistat: Development of Analogues with ϖ-Amino Acids Linking Critical Binding Segments

Volume: 12 Issue: 3

Author(s): Deborah L. Heyl, Shakila Tobwala, Leo Solomon Lucas, A. Dammika Nandanie, Rebecca W. Himm, Jennifer Kappler, Elizabeth J. Blaney, Jason Groom, Jeffrey Asbill, Jonathan K. Nzoma, Cara Jarosz,, Hanna Palamma and Stephen E. Schullery

Affiliation:

Keywords: amylase, inhibitor, tendamistat, binding segment, linker

Abstract: Peptide analogues of Tendamistat which include the most essential residues linked by novel w-amino acids (X,Y,Z: H2N-(CH2)n-CO2H, where n=2-10) were designed, synthesized (Ac-Tyr15-X-Trp18-Arg19-Tyr20-Y-Thr55-Z-Asp58- Gly59-Tyr60-Ile61-Gly62-NH2), and analyzed for α-amylase inhibitory activity. Native dipeptide spacers sometimes were left intact at X and Z. Analogues demonstrated competitive inhibition with Ki values ranging from 23 to 767 μM. 8- Aminooctanoic acid was the optimal linker at Y, while longer linkers were favored at the other positions.

Cite this article as:

Heyl L. Deborah, Tobwala Shakila, Lucas Solomon Leo, Nandanie Dammika A., Himm W. Rebecca, Kappler Jennifer, Blaney J. Elizabeth, Groom Jason, Asbill Jeffrey, Nzoma K. Jonathan, Jarosz, Cara, Palamma Hanna and Schullery E. Stephen, Peptide Inhibitors of a-Amylase Based on Tendamistat: Development of Analogues with ϖ-Amino Acids Linking Critical Binding Segments, Protein & Peptide Letters 2005; 12 (3) . https://dx.doi.org/10.2174/0929866053587110