Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments

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; Stephen E. Schullery

doi:10.2174/0929866053587110

Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments

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
, Stephen E. Schullery

Division of Gastroenterology

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Peptide analogues of Tendamistat which include the most essential residues linked by novel ω-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-Ile ⁶¹-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 K_i 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.

Original language	English
Pages (from-to)	275-280
Number of pages	6
Journal	Protein and Peptide Letters
Volume	12
Issue number	3
DOIs	https://doi.org/10.2174/0929866053587110
State	Published - Apr 2005

Keywords

Binding segment
Inhibitor
Linker
Tendamistat
α-amylase

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10.2174/0929866053587110

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Heyl, D. L., Tobwala, S., Lucas, L. S., Nandanie, A. D., Himm, R. W., Kappler, J., Blaney, E. J., Groom, J., Asbill, J., Nzoma, J. K., Jarosz, C., Palamma, H., & Schullery, S. E. (2005). Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments. Protein and Peptide Letters, 12(3), 275-280. https://doi.org/10.2174/0929866053587110

@article{af293aac23e448b1ac27c976a2742ba1,

title = "Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments",

abstract = "Peptide analogues of Tendamistat which include the most essential residues linked by novel ω-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-Ile 61-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.",

keywords = "Binding segment, Inhibitor, Linker, Tendamistat, α-amylase",

author = "Heyl, \{Deborah L.\} and Shakila Tobwala and Lucas, \{Leo Solomon\} and Nandanie, \{A. Dammika\} and Himm, \{Rebecca W.\} and Jennifer Kappler and Blaney, \{Elizabeth J.\} and Jason Groom and Jeffrey Asbill and Nzoma, \{Jonathan K.\} and Cara Jarosz and Hanna Palamma and Schullery, \{Stephen E.\}",

year = "2005",

month = apr,

doi = "10.2174/0929866053587110",

language = "English",

volume = "12",

pages = "275--280",

journal = "Protein and Peptide Letters",

issn = "0929-8665",

number = "3",

}

Heyl, DL, Tobwala, S, Lucas, LS, Nandanie, AD, Himm, RW, Kappler, J, Blaney, EJ, Groom, J, Asbill, J, Nzoma, JK, Jarosz, C, Palamma, H & Schullery, SE 2005, 'Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments', Protein and Peptide Letters, vol. 12, no. 3, pp. 275-280. https://doi.org/10.2174/0929866053587110

TY - JOUR

T1 - Peptide inhibitors of α-amylase based on tendamistat

T2 - Development of analogues with ω-amino acids linking critical binding segments

AU - Heyl, Deborah L.

AU - Tobwala, Shakila

AU - Lucas, Leo Solomon

AU - Nandanie, A. Dammika

AU - Himm, Rebecca W.

AU - Kappler, Jennifer

AU - Blaney, Elizabeth J.

AU - Groom, Jason

AU - Asbill, Jeffrey

AU - Nzoma, Jonathan K.

AU - Jarosz, Cara

AU - Palamma, Hanna

AU - Schullery, Stephen E.

PY - 2005/4

Y1 - 2005/4

N2 - Peptide analogues of Tendamistat which include the most essential residues linked by novel ω-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-Ile 61-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.

AB - Peptide analogues of Tendamistat which include the most essential residues linked by novel ω-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-Ile 61-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.

KW - Binding segment

KW - Inhibitor

KW - Linker

KW - Tendamistat

KW - α-amylase

UR - https://www.scopus.com/pages/publications/20144363563

U2 - 10.2174/0929866053587110

DO - 10.2174/0929866053587110

M3 - Article

C2 - 15777278

AN - SCOPUS:20144363563

SN - 0929-8665

VL - 12

SP - 275

EP - 280

JO - Protein and Peptide Letters

JF - Protein and Peptide Letters

IS - 3

ER -

Peptide inhibitors of α-amylase based on tendamistat: Development of analogues with ω-amino acids linking critical binding segments

Abstract

Keywords

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