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Literature summary for 3.1.1.4 extracted from

  • Mouchlis, V.D.; Mavromoustakos, T.M.; Kokotos, G.
    Design of new secreted phospholipase A2 inhibitors based on docking calculations by modifying the pharmacophore segments of the FPL67047XX inhibitor (2010), J. Comput. Aided Mol. Des., 24, 107-115.
    View publication on PubMed

Application

Application Comment Organism
drug development design of new analogues with enhanced binding energy in the GIIA sPLA2 active site by systematic modifications of the pharmacophore segments of the FPL67047XX inhibitor Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(3S)-4-[(4-benzylphenyl)sulfanyl]-3-[(7-phenylheptanoyl)amino]butane-1-sulfonic acid bioisosteric replacements, binding energy of -22.05 kJ/mol Homo sapiens
(3S)-4-[(4-benzylphenyl)sulfanyl]-3-[(7-phenylheptanoyl)amino]butyl phosphonic acid bioisosteric replacements, binding energy of -19.76 kJ/mol Homo sapiens
(3S)-4-[(4-benzylphenyl)sulfanyl]-3-[[7-(4-hydroxyphenyl)heptanoyl]amino]butane-1-sulfonic acid bioisosteric replacements, molecular structure is characterized by a chiral centre of absolute (R)-configuration, four carbons in the R1 chain, a hydroxyl group as a substituent in the para-position of the phenyl ring in R1 chain and a sulphonate group instead of the carboxylate group, indicates the highest binding energy (-29.1 kJ/mol) than all the other analogues and the prototype Homo sapiens
(4R)-5-[(4-benzylphenyl)sulfanyl]-4-[(7-phenylheptanoyl)amino]pentanoic acid (R)-configuration of FPL67047XX, binding energy of -19.5 kJ/mol Homo sapiens
(4S)-5-[(4-benzylphenyl)sulfanyl]-4-[(5-phenylpentanoyl)amino]pentanoic acid decreased carbon chain length between the amide group and the aromatic ring of the R1 chain, binding energy of -22.02 kJ/mol Homo sapiens
(4S)-5-[(4-benzylphenyl)sulfanyl]-4-[[7-(4-hydroxyphenyl)heptanoyl]amino]pentanoic acid substituents in the para-position of the aromatic ring R1, higher binding energy (-27.61 kJ/mol) than the prototype and all the other analogues except structure 9 Homo sapiens
(4S)-5-[(4-benzylphenyl)sulfanyl]-4-[[7-(4-methoxyphenyl)heptanoyl]amino]pentanoic acid substituents in the para-position of the aromatic ring R1, binding energy of -22.23 kJ/mol Homo sapiens
(4S)-5-[(4-benzylphenyl)sulfanyl]-4-[[7-(4-nitrophenyl)heptanoyl]amino]pentanoic acid substituents in the para-position of the aromatic ring R1, binding energy of -20.25 kJ/mol Homo sapiens
FPL67047XX used as a prototype structure with a binding energy of -18.96 kJ/mol Homo sapiens
additional information the (R)-enantiomer presents higher binding energy than the (S)-FPL67047XX inhibitor. The decrease of the number of carbon atoms of the R1 chain increases the binding energy. The insertion of a hydroxyl group in the para-position of the aromatic ring of R1 chain increases the binding energy. The optimum number of carbon atoms in the amino acid part of the ligand is three. The sulphonate group presents the most favourable interactions in comparison with carboxylate and phosphonate groups and the aromatic chains are essential for the binding activity because the phenyl rings participate in tilted-T aromatic (Pi–Pi) stacking and aromatic/aliphatic interactions Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P14555
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-

Synonyms

Synonyms Comment Organism
GIIA sPLA2
-
Homo sapiens
secreted phospholipase A2
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Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000013
-
-
Homo sapiens FPL67047XX