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

3 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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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

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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

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DO - 10.2174/0929866053587110

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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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