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Literature summary for 2.3.1.97 extracted from

  • Hutton, J.A.; Goncalves, V.; Brannigan, J.A.; Paape, D.; Wright, M.H.; Waugh, T.M.; Roberts, S.M.; Bell, A.S.; Wilkinson, A.J.; Smith, D.F.; Leatherbarrow, R.J.; Tate, E.W.
    Structure-based design of potent and selective Leishmania N-myristoyltransferase inhibitors (2014), J. Med. Chem., 57, 8664-8670.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
in complex with inhibitors N-[5-[(4R)-1-[(3R)-3-amino-4-(4-chlorophenyl)butanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]-2-chlorophenyl]-2-(4-fluorophenyl)acetamide and N-[2-chloro-5-[(3S,4R)-1-[4-(4-chlorophenyl)-3-hydroxybutanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]phenyl]-2-(4-fluorophenyl)acetamide. The para-fluorophenyl acetamide in ortho-position to the chlorine atom in compound N-[5-[(4R)-1-[(3R)-3-amino-4-(4-chlorophenyl)butanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]-2-chlorophenyl]-2-(4-fluorophenyl)acetamide significantly improves potency. This could potentially introduce hydrogen bonding between the acetamide carbonyl and Tyr345 and Asn376 and allow the compound to extend into a hydrophobic pocket Leishmania major

Inhibitors

Inhibitors Comment Organism Structure
N-[2-chloro-5-[(3S,4R)-1-[4-(4-chlorophenyl)-3-hydroxybutanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]phenyl]-2-(4-fluorophenyl)acetamide inhibitor shows good selectiviy over the human enzyme Leishmania donovani
N-[2-chloro-5-[(3S,4R)-1-[4-(4-chlorophenyl)-3-hydroxybutanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]phenyl]-2-(4-fluorophenyl)acetamide inhibitor shows good selectiviy over the human enzyme Leishmania major
N-[5-[(4R)-1-[(3R)-3-amino-4-(4-chlorophenyl)butanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]-2-chlorophenyl]-2-(4-fluorophenyl)acetamide inhibitor shows good selectiviy over the human enzyme Leishmania donovani
N-[5-[(4R)-1-[(3R)-3-amino-4-(4-chlorophenyl)butanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]-2-chlorophenyl]-2-(4-fluorophenyl)acetamide inhibitor shows good selectiviy over the human enzyme Leishmania major

Organism

Organism UniProt Comment Textmining
Leishmania donovani D0AB09
-
-
Leishmania major Q4Q5S8
-
-

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000016
-
pH not specified in the publication, temperature not specified in the publication Leishmania donovani N-[5-[(4R)-1-[(3R)-3-amino-4-(4-chlorophenyl)butanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]-2-chlorophenyl]-2-(4-fluorophenyl)acetamide
0.000059
-
pH not specified in the publication, temperature not specified in the publication Leishmania donovani N-[2-chloro-5-[(3S,4R)-1-[4-(4-chlorophenyl)-3-hydroxybutanoyl]-4-(hydroxymethyl)pyrrolidin-3-yl]phenyl]-2-(4-fluorophenyl)acetamide