Acetylated derivatives of C-methylated analogues of spermidine: synthesis and interaction with N1-acetylpolyamine oxidase

2018 ◽  
Vol 28 (5) ◽  
pp. 479-481 ◽  
Author(s):  
Maxim A. Khomutov ◽  
Mervi T. Hyvönen ◽  
Alina R. Simonian ◽  
Janne Weisell ◽  
Jouko Vepsäläinen ◽  
...  
Keyword(s):  
Derivatives Of ◽  
Acetylpolyamine Oxidase

scholarly journals Controlling the regioselectivity and stereospecificity of FAD-dependent polyamine oxidases with the use of amine-attached guide molecules as conformational modulators

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Tuomo A. Keinänen ◽  
Nikolay Grigorenko ◽  
Alex R. Khomutov ◽  
Qingqiu Huang ◽  
Anne Uimari ◽  
...  
Keyword(s):  
Catalytic Properties ◽  
Isonicotinic Acid ◽  
The Novel ◽  
Fundamental Properties ◽  
Competitive Inhibitors ◽  
Substrate Mixtures ◽  
Derivatives Of ◽  
Acetylpolyamine Oxidase ◽  
Acyl Derivatives ◽  
Polyamine Oxidases

Enzymes generally display strict stereospecificity and regioselectivity for their substrates. Here by using FAD-dependent human acetylpolyamine oxidase (APAO), human spermine (Spm) oxidase (SMOX) and yeast polyamine oxidase (Fms1), we demonstrate that these fundamental properties of the enzymes may be regulated using simple guide molecules, being either covalently attached to polyamines or used as a supplement to the substrate mixtures. APAO, which naturally metabolizes achiral N1-acetylated polyamines, displays aldehyde-controllable stereospecificity with chiral 1-methylated polyamines, like (R)- and (S)-1-methylspermidine (1,8-diamino-5-azanonane) (1-MeSpd). Among the novel N1-acyl derivatives of MeSpd, isonicotinic acid (P4) or benzoic acid (Bz) with (R)-MeSpd had Km of 3.6 ± 0.6/1.2 ± 0.7 µM and kcat of 5.2 ± 0.6/4.6 ± 0.7 s−1 respectively, while N1-AcSpd had Km 8.2 ± 0.4 µM and kcat 2.7 ± 0.0 s−1. On the contrary, corresponding (S)-MeSpd amides were practically inactive (kcat < 0.03 s−1) but they retained micromole level Km for APAO. SMOX did not metabolize any of the tested compounds (kcat < 0.05 s−1) that acted as non-competitive inhibitors having Ki ≥ 155 µM for SMOX. In addition, we tested (R,R)-1,12-bis-methylspermine (2,13-diamino-5,10-diazatetradecane) (R,R)-(Me2Spm) and (S,S)-Me2Spm as substrates for Fms1. Fms1 preferred (S,S)- to (R,R)-diastereoisomer, but with notably lower kcat in comparison with spermine. Interestingly, Fms1 was prone to aldehyde supplementation in its regioselectivity, i.e. the cleavage site of spermidine. Thus, aldehyde supplementation to generate aldimines or N-terminal substituents in polyamines, i.e. attachment of guide molecule, generates novel ligands with altered charge distribution changing the binding and catalytic properties with polyamine oxidases. This provides means for exploiting hidden capabilities of polyamine oxidases for controlling their regioselectivity and stereospecificity.

Physical Properties of TCNQ Salts with N-Methyl Derivatives of Pyridine

1982 ◽  
Vol 85 (1) ◽  
pp. 257-263 ◽  
Author(s):  
A. Graja ◽  
M. Przybylski ◽  
B. Butka ◽  
R. Swietlik
Keyword(s):  
Physical Properties ◽  
Methyl Derivatives ◽  
Derivatives Of

Diorganyl Derivatives of Tellurium(IV) (σ-Telluranes of R 2 TeX 2 Type)

2002 ◽  
Vol 23 (2) ◽  
pp. 125-207 ◽  
Author(s):  
Igor D. Sadekov ◽  
Alexander V. Zakharov ◽  
Alexander A. Maksimenko
Keyword(s):  
Derivatives Of

Hindered rotation around the amide bond in a series of derivatives of 2-acetamidothiophenes

1991 ◽  
Vol 88 ◽  
pp. 689-707 ◽  
Author(s):  
P Andriamadio ◽  
D Nicole ◽  
A Cartier ◽  
M Wierzbicki ◽  
G Kirsch
Keyword(s):  
Amide Bond ◽  
Hindered Rotation ◽  
Derivatives Of
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