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

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 - https://www.scopus.com/pages/publications/0035083882

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 -