Carbonic anhydrase activators. Activation of the membrane-associated isoform XV with amino acids and amines

被引:12
作者
Innocenti, Alessio [1 ]
Hilvo, Mika [2 ,3 ,4 ]
Parkkila, Seppo [2 ,3 ,5 ]
Scozzafava, Andrea [1 ]
Supuran, Claudiu T. [1 ]
机构
[1] Univ Florence, Chim Bioorgan Lab, I-50019 Florence, Italy
[2] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland
[3] Tampere Univ Hosp, Tampere, Finland
[4] VTT Tech Res Ctr Finland, FI-02044 Espoo, Finland
[5] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland
关键词
Carbonic anhydrase; Isoform XV; Amine; Amino acid; Enzyme activator; ISOZYME-II; ACTIVE-SITE; CRYSTALLOGRAPHIC ANALYSIS; L-HISTIDINE; CA-XIII; IV; XIV; INHIBITION; VII; VA;
D O I
10.1016/j.bmcl.2009.05.026
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
An activation study of the membrane-associated carbonic anhydrase (CA, EC 4.2.1.1) isoform XV with a series of natural and non-natural amino acids and aromatic/heterocyclic amines is reported. Murine CA XV was strongly activated by some amino acids (D-Phe, L-/D-DOPA, D-Trp, L-Tyr) and amines (dopamine, serotonin, L-adrenaline and 4-(2-aminoethyl)-morpholine) with activation constants in the range of 4.0-9.5 mu M. L-/D-His, L-Phe, histamine and several other heterocyclic amines showed less efficient activation (K(A)s in the range of 11.6-33.4 mu M). The activation pro. le of CA XV is quite different from that of the cytosolic isoforms CA I and II or the membrane-associated CA IV. All mammalian isoforms CA I-XV are thus characterized for their interaction with this set of amino acid and amine activators, some of which are biogenic amines or neurotransmitters present in sufficiently high amounts in various tissues for exerting significant biologic responses. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:3430 / 3433
页数:4
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