Peptide inhibitors of alpha-amylase based on tendamistat: development of analogues with omega-amino acids linking critical binding segments.
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.
Heyl
Deborah L
DL
Department of Chemistry, Eastern Michigan University, Ypsilanti, MI 48197, USA. dheylcle@emich.edu
Tobwala
Shakila
S
Lucas
Leo Solomon
LS
Nandanie
A Dammika
AD
Himm
Rebecca W
RW
Kappler
Himm Jennifer
HJ
Blaney
Elizabeth J
EJ
Groom
Jason
J
Asbill
Jeffrey
J
Nzoma
Jonathan K
JK
Jarosz
Cara
C
Palamma
Hanna
H
Schullery
Stephen E
SE
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
D000596:Amino Acids; D004791:Enzyme Inhibitors; D010455:Peptides; D000516:alpha-Amylases; C030526:tendamistate