| 000 | 03803nlm1a2200493 4500 | ||
|---|---|---|---|
| 001 | 662004 | ||
| 005 | 20231030041806.0 | ||
| 035 | _a(RuTPU)RU\TPU\network\33137 | ||
| 035 | _aRU\TPU\network\31754 | ||
| 090 | _a662004 | ||
| 100 | _a20200424a2020 k y0engy50 ba | ||
| 101 | 0 | _aeng | |
| 135 | _adrcn ---uucaa | ||
| 181 | 0 | _ai | |
| 182 | 0 | _ab | |
| 200 | 1 |
_aThe investigation of structure–activity relationship of polyamine-targeted synthetic compounds from different chemical groups _fS. P. Syatkin, E. V. Neborak, A. I. Khlebnikov [et al.] |
|
| 203 |
_aText _celectronic |
||
| 300 | _aTitle screen | ||
| 330 | _aThe polyamine (PA) metabolism is involved in cell proliferation and differentiation. Increased cellular PA levels are observed in different types of cancers. Products of PA oxidation induce apoptosis in cancer cells. These observations open a perspective to exploit the enzymes of PA catabolism as a target for anticancer drug design. The substances capable to enhance PA oxidation may become potential anticancer agents. The goal of our study was to explore how the mode of ligand binding with a PA catabolic enzyme is associated with its stimulatory or inhibitory effect upon PA oxidation. Murine N1-acetylpolyamine oxidase (5LFO) crystalline structure was used for molecular docking with ligands of various chemical structures. In vitro experiments were carried out to evaluate the action of the tested compounds upon PA oxidative deamination in a cell-free test system from rat liver. Two amino acid residues (Aps211 and Tyr204) in the structure of 5LFO were found to be significant for binding with the tested compounds. 19 out of 51 screened compounds were activators and 17 were inhibitors of oxidative deamination of PA. Taken together, these results enabled to construct a recognition model with characteristic descriptors depicting activators and inhibitors. The general tendency indicated that a strong interaction with Asp211 or Tyr204 was rather typical for activators. The understanding of how the structure determines the binding mode of compounds with PA catabolic enzyme may help in explanation of their structure–activity relationship and thus promote structure-based drug design. | ||
| 333 | _aРежим доступа: по договору с организацией-держателем ресурса | ||
| 461 | _tAmino Acids | ||
| 463 |
_tVol. 52 _v[P. 199-211] _d2020 |
||
| 610 | 1 | _aэлектронный ресурс | |
| 610 | 1 | _aтруды учёных ТПУ | |
| 610 | 1 | _apolyamines | |
| 610 | 1 | _apolyamine catabolism | |
| 610 | 1 | _apolyamine-targeted agents | |
| 610 | 1 | _amolecular docking | |
| 610 | 1 | _astructure-activity relationship | |
| 610 | 1 | _aполиамины | |
| 610 | 1 | _aкатаболизм | |
| 610 | 1 | _aмолекулярная стыковка | |
| 701 | 1 |
_aSyatkin _bS. P. _gSergey Pavlovich |
|
| 701 | 1 |
_aNeborak _bE. V. _gEkaterina Vladislavovna |
|
| 701 | 1 |
_aKhlebnikov _bA. I. _cChemist _cProfessor of Tomsk Polytechnic University _f1963- _gAndrey Ivanovich _2stltpush _3(RuTPU)RU\TPU\pers\33927 |
|
| 701 | 1 |
_aKomarova _bM. V. _gMarina Vladimirovna |
|
| 701 | 1 |
_aShevkun _bN. A. _gNataliya Aleksandrovna |
|
| 701 | 1 |
_aKravtsov _bE. G. _gEduard Georgievich |
|
| 701 | 1 |
_aBlagonravov _bM. L. _gMikhail Lvovich |
|
| 701 | 1 |
_aAgostinelli _bE. _gEnzo |
|
| 712 | 0 | 2 |
_aНациональный исследовательский Томский политехнический университет _bИнженерная школа новых производственных технологий _bНаучно-образовательный центр Н. М. Кижнера _h7872 _2stltpush _3(RuTPU)RU\TPU\col\23556 |
| 801 | 2 |
_aRU _b63413507 _c20200424 _gRCR |
|
| 856 | 4 | _uhttps://doi.org/10.1007/s00726-019-02778-3 | |
| 942 | _cCF | ||