Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks

J. H. McKie; J. Garforth; R. Jaouhari; C. Chan; H. Yin; T. Besheya; A. H. Fairlamb; K. T. Douglas

doi:10.1007/s007260170055

Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks

J. H. McKie, J. Garforth, R. Jaouhari, C. Chan, H. Yin, T. Besheya, A. H. Fairlamb, K. T. Douglas

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

14 Citations (Scopus)

Abstract

By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide with a K_i value of 2.4 μM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

Original language	English
Pages (from-to)	145-153
Number of pages	9
Journal	Amino Acids
Volume	20
Issue number	2
DOIs	https://doi.org/10.1007/s007260170055
Publication status	Published - Mar 2001

Keywords

Amino acids
Antiparasitics
Drug leads
Glutathione
Leishmaniasis
Trypanosomiasis

ASJC Scopus subject areas

Biochemistry
Organic Chemistry
Clinical Biochemistry

Access to Document

10.1007/s007260170055

Cite this

@article{8419ff4c46994396bb5920e80e2e16a3,

title = "Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks",

abstract = "By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide with a Ki value of 2.4 μM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.",

keywords = "Amino acids, Antiparasitics, Drug leads, Glutathione, Leishmaniasis, Trypanosomiasis",

author = "McKie, {J. H.} and J. Garforth and R. Jaouhari and C. Chan and H. Yin and T. Besheya and Fairlamb, {A. H.} and Douglas, {K. T.}",

year = "2001",

month = mar,

doi = "10.1007/s007260170055",

language = "English",

volume = "20",

pages = "145--153",

journal = "Amino Acids",

issn = "0939-4451",

publisher = "Springer Verlag",

number = "2",

}

TY - JOUR

T1 - Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate

T2 - potential rational drug design lead frameworks

AU - McKie, J. H.

AU - Garforth, J.

AU - Jaouhari, R.

AU - Chan, C.

AU - Yin, H.

AU - Besheya, T.

AU - Fairlamb, A. H.

AU - Douglas, K. T.

PY - 2001/3

Y1 - 2001/3

N2 - By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide with a Ki value of 2.4 μM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

AB - By introducing cationic charge sites novel peptide lead inhibitor structures for trypanothione reductase have been designed using molecular modelling methods. The inhibitors showed reversible, linear competitive inhibition and the strongest peptide inhibitor to date was found to be N-benzyloxycarbonyl-Ala-Arg-Arg-4-methoxy-β-naphthylamide with a Ki value of 2.4 μM and a selectivity for parasitic enzyme (trypanothione reductase) over the host enzyme (human glutathione reductase) of over 3 orders of magnitude.

KW - Amino acids

KW - Antiparasitics

KW - Drug leads

KW - Glutathione

KW - Leishmaniasis

KW - Trypanosomiasis

UR - http://www.scopus.com/inward/record.url?scp=0035083882&partnerID=8YFLogxK

U2 - 10.1007/s007260170055

DO - 10.1007/s007260170055

M3 - Article

C2 - 11332449

AN - SCOPUS:0035083882

SN - 0939-4451

VL - 20

SP - 145

EP - 153

JO - Amino Acids

JF - Amino Acids

IS - 2

ER -

Specific peptide inhibitors of trypanothione reductase with backbone structures unrelated to that of substrate: potential rational drug design lead frameworks

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this