Wyniki wyszukiwania - BazTech

1

Polypharmacology – a challenge for current drug design approaches

Podlewska Sabina, Kurczab Rafał

Science, Technology and Innovation

|

2019

|

Vol. 6, no. 3

19--23

EN

Drug design process faces many challenges, and the most important ones are connected with side effects. Finding compounds that possess affinity towards target of interest is relatively simple; however, an approach one disease-one target is now making space for the search of polypharmacological ligands, where activity towards several proteins is considered at one time. Such proteins are not always the target ones, but very often such panels include also anti-targets, interaction with which is not desired, due to the side effects that may occur upon such contact. In the study, we examined ligands of four G protein-coupled receptors, forming antipsychotic profile: dopamine receptor D2, serotonin receptors 5-HT2A, 5-HT2C (anti-target), and 5-HT6. Number of ligands belonging to particular activity groups, as well as the selected compound structures are examined in detail. Also compound similarity between sets of different activity groups is analysed, giving a picture of difficulty of constructing molecular modeling methodologies that can help in the search of compounds with desired activity profile.

2

Algorytm haszowania geometrycznego w dokowaniu molekularnym

Pacholczyk M., Bereska D.

Zeszyty Naukowe. Automatyka / Politechnika Śląska

|

2006

|

z. 145

157-162

PL

W pracy przedstawiono implementację oraz wstępne wyniki działania zmodyfikowanego algorytmu wizji komputerowej - haszowania geometrycznego zastosowanego w problemie dokowania molekularnego. Dokowanie molekularne w ujęciu przedstawionym w pracy jest problemem znalezienia najlepszego dopasowania struktury przestrzennej białka oraz mniejszej molekuły - ligandu (molekuły lekopodobnej). Jako model interakcji białko ligand zastosowano powierzchnie interakcji - stanowiących geometryczną reprezentację zbioru reguł rządzących oddziaływaniami na poziomie molekularnym (wiązania wodorowe, oddziaływania hydrofobowe). Właściwości algorytmu zostały sprawdzone podczas próby rekonstrukcji naturalnego dopasowania struktury izomerazy oraz ligandu SO4, pochodzących z kompleksu o oznaczeniu 5TIM (PDB).

EN

The paper presents an implementation and preliminary results obtained with modified computer vision algorithm called geometric hashing applied to the problem of molecular docking. Molecular docking as presented here is the problem of finding the best possible matching between protein structure and a ligand (typically a smaller, drag like molecule). As a model for protein - ligand interaction we use the interaction surfaces - geometric representation of rules governing intramolecular interactions (hydrogen bonds, hydrofobic interactions). We tested our method trying to reconstruct native binding pose of the SO4 ligand and isomerase in 5TIM (PDB) complex.

3

Luminescent materials, recognition phases of the chemical sensors and heterogeneous catalysts prepared by sol-gel method

Kłonkowski A. M.

Materials Science

|

2002

|

Vol. 20, No. 1

57-70

EN

The sol-gel process enables one to prepare oxide xerogels at room temperature. By using this method, it is possible to encapsulate a wide variety of organic, complex (organometallic) molecules and metallic nanoparticles stabilized by organic ligands in the inorganic or inorganic/organic hybrid matrix. Studies of this new type of inorganic/organic composite have evolved towards the deliberate doping of the supramolecular species. This review gives three examples of how doped xerogel materials prepared by the sol-gel method are emerging as an important means of producing new materials. The first part of this review is devoted to luminescent materials which are based on the antenna effect and are composed of Eu(III) complex (luminescence centre) entrapped in xerogel matrix. In this case results of the experiments concerning the coordination sphere composition show that a cryptand ligand with aromatic groups and an aromatic co-ligand, settle efficient action the antenna effect and isolate the central ion from each efficient quenchers, as e.g. water molecules. Secondly, silica xerogel samples with entrapped series of three fluorescent chemosensors of the Ant-R-Ant type, where Ant is an anthryl group and R is a receptor (spacer) with donor atoms, were prepared as chemical recognition phases. The recognition phase with fluorosensor of the type Ant- N-O-O-N-Ant, where N and O are donor atoms, can be regenerated many times and seems to be most promising system for the fluorescent chemical sensor. In the third part of this paper, ligand protected metal nanoclusters as immobilized catalysts are the point of interest. This type of heterogeneous catalysts are much less investigated than the bare metal particles on supports. The main interest is focused on the function of the ligands.

4

Receptory sprzężone z białkami G (GPCR) ; struktura i oddziaływania z bioligandami

Ciarkowski J., Czaplewski C., Kaźmierkiewicz R., Politowska E.

Wiadomości Chemiczne

|

1998

|

[Z] 52, 5-6

431-447

EN

G protein-coupled receptors (GPCRs) from the largest superfamily, having over 1000 members, of integral membrane proteins sharing the following features: (i) All members from 7 hydrophobic a-helices of ~38 A (25 amino acids, 7 turns) along a single chain. The consecutive helices pass the membrane forth and back, starting from the extracellular side, to from a heptahelical transmembrane domain. This arrangement implicates 6 interhelical loops, whereof the even ones plus the N-terminus create the receptor's extracellular domain while the odd ones plus the C-terminus from its intracellular domain. (ii) All GPCRs are stimulated by extracellular signals of miscellaneous character. (iii) Stimulated GPCRs pass the extracellular signal via their transmembrane and intracellular domains to the cytosolic peripheral heterotrimeric GTP/GDP - binding proteins (G proteins), mediating the signal's further transduction to various cellular second messenger systems. A current status of structural studies on GPCRs, consisting of low ~7.5 A resolution experimental structures and supplementary molecular modelling, is presented. Subsequently, some results of author's own work on modelling essential interactions between the V2 vaasopressin renal receptor (V2R) and its agonists [Arg8] Vasopressin (AVP), [d-Arg8] Vasopressin (DAVP), and both the peptide desGly9 -[Mca1, D-Ile2, Ile4]AVP and the nonpeptide antagonist OPC-31260, are discussed. Finally perspectives for future developments are outlined.