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Peptide inhibitors of alpha-amylase based on tendamistat: development of analogues with omega-amino acids linking critical binding segments

Deborah L Heyl 1, Shakila Tobwala, Leo Solomon Lucas, A Dammika Nandanie, Rebecca W Himm, Himm Jennifer Kappler, Elizabeth J Blaney, Jason Groom, Jeffrey Asbill, Jonathan K Nzoma, Cara Jarosz, Hanna Palamma, Stephen E Schullery


Peptide analogues of Tendamistat which include the most essential residues linked by novel omega-amino acids (X,Y,Z: H2N-(CH2)n-CO(2)H, where n=2-10) were designed, synthesized (Ac-Tyr(15)-X-Trp(18)-Arg(19)-Tyr(20)-Y-Thr(55)-Z-Asp(58)-Gly(59)-Tyr(60)-Ile(61)-Gly(62)-NH2), and analyzed for alpha-amylase inhibitory activity. Native dipeptide spacers sometimes were left intact at X and Z. Analogues demonstrated competitive inhibition with K(i) values ranging from 23 to 767 microM. 8-Aminooctanoic acid was the optimal linker at Y, while longer linkers were favored at the other positions.
  • Arthroscopic Association of North America
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  • American Osteopathic Association
  • American Academy of Orthopedic Surgeons