title: Peptide inhibitors of alpha-amylase based on tendamistat: development of analogues with omega-amino acids linking critical binding segments.
abstract: 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.
authors.affiliation: Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA. dheylcle@emich.edu
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Heyl
authors.forename: Shakila
authors.initials: S
authors.lastname: Tobwala
authors.forename: Leo Solomon
authors.initials: LS
authors.lastname: Lucas
authors.forename: A Dammika
authors.initials: AD
authors.lastname: Nandanie
authors.forename: Rebecca W
authors.initials: RW
authors.lastname: Himm
authors.forename: Himm Jennifer
authors.initials: HJ
authors.lastname: Kappler
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Blaney
authors.forename: Jason
authors.initials: J
authors.lastname: Groom
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Asbill
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Nzoma
authors.forename: Cara
authors.initials: C
authors.lastname: Jarosz
authors.forename: Hanna
authors.initials: H
authors.lastname: Palamma
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Schullery
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D000516:alpha-Amylases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000596:Amino Acids; D004791:Enzyme Inhibitors; D010455:Peptides; D000516:alpha-Amylases; C030526:tendamistate