Structure Activity
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2022 ◽  
Vol 19 (2) ◽  
pp. 2022
Tapan Kumar Baishya ◽  
Bijit Bora ◽  
Pawan Chetri ◽  
Upashana Gogoi

Topological indices (TI) (descriptors) of a molecular graph are very much useful to study various physiochemical properties. It is also used to develop the quantitative structure-activity relationship (QSAR), quantitative structure-property relationship (QSPR) of the corresponding chemical compound. Various techniques have been developed to calculate the TI of a graph. Recently a technique of calculating degree-based TI from M-polynomial has been introduced. We have evaluated various topological descriptors for 3-dimensional TiO2 crystals using M-polynomial. These descriptors are constructed such that it contains 3 variables (m, n and t) each corresponding to a particular direction. These 3 variables facilitate us to deeply understand the growth of TiO2 in 1 dimension (1D), 2 dimensions (2D), and 3 dimensions (3D) respectively. HIGHLIGHTS Calculated degree based Topological indices of a 3D crystal from M-polynomial A relation among various Topological indices is established geometrically Variations of Topological Indices along three dimensions (directions) are shown geometrically Harmonic index approximates the degree variation of oxygen atom

2022 ◽  
Vol 116 (1) ◽  
pp. 20-27
Vladimír Pliska ◽  
Antonín Pařízek ◽  
Martin Flegel

From the fifties to the seventies of the last century, the neurohypophyseal peptides oxytocin and vasopressin constituted one of the main research areas at the Institute of Organic Chemistry and Biochemistry in Prague (IOCB). A significant contribution to this area is associated with the names of František Šorm, director of the said institute, and Josef Rudinger, head of the institute's peptide laboratory. At that time, newly developed research tools enabled to synthesize structural analogues of these hormones in numerous laboratories worldwide and hence to investigate the structure-activity relationships within this peptide group. Contributions of single peptide-chain positions to the respective biological activities were identified which opened a possibility to rationalize a design of peptides with a combination of changes in several positions. Several clinically interesting peptides were synthesized in the late 1960s at the IOCB and employed as therapeutics: [(Gly)3-Cys1,Lys8]-vasopressin (Glypressin Ferring®, Terli­pressin INN), 1-deamino-8-ᴅ-arginine vasopressin (Desmopressin INN, dDAVP), and later the uterotonics carbetocin (INN), widely used in obstetrics to prevent postpartum haemorrhage. Since the industrial production of peptide therapeutics was scarcely possible under the conditions of socialist economy in Czechoslovakia as well as in other countries under the Soviet influence, F. Šorm agreed to use the already established scientific contacts of IOCB with the Swedish pharmaceutical company Ferring AB and to transfer the production licences to Sweden. The license agreements were signed in 1969 and led to a quick spread of dDAVP in the substitution therapy of the central form of diabetes insipidus and, moreover, contributed to a fast upsurge of the Ferring company. Somewhat later, Glypressin was produced as a therapeutic with a prolonged action in cases of cardiovascular collapse. Contacts between Prague peptide chemists and the Ferring company lasted on a rather informal base until the end of the 1980s. After the fall of the totalitarian regime in Czechoslovakia in 1990, Ferring started a joint-venture collaboration with the newly organized Czech company Léčiva st.p. Praha in a newly established group Prague Polypeptide Institute spol. s. r.o. (later Ferring-Léčiva A.S.). A substantial part of the peptide-production capacities was then transferred to new buildings in Prague.

2022 ◽  
Maroof A. Hegazy ◽  
Rasha Ghoneim ◽  
Hend A. Ezzat ◽  
Heba Y. Zahran ◽  
Ibrahim S. Yahia ◽  

Abstract On polytetrafluoroethylene (PTFE) polymer nanocomposites coated with basically two metal oxides (MOs), SiO2 and ZnO, as well as a mixture of the two MOs, density functional theory (DFT) computations were performed. The B3LYPL/LAN2DZ model was used to evaluate PTFE polymer nano composites suggested model structures. The physical and electrical properties of PTFE modified on surface with ZnO and SiO2 coated layer by layer change Total dipole moment (TDM) and HOMO/LUMO band gap energy ∆Eto be 13.0082 Debye and 0.6889 eV, respectively. Moreover, TDM and band gap energy (∆E) improved to 10.6053 Debye and 0.2727 eV, respectively, when the nanofiller was increased to 8 atoms. In addition, the results of the Molecular Electrostatic Potential (MESP) and the Quantitative Structure Activity Relationship (QSAR) showed that PTFE coated with ZnO and SiO2 improved electrical characteristics and thermal stability. As PTFE coated with ZnO and SiO2 layer by layer, all stability characteristics, including electrical and thermal stability, were enhanced. The improved PTFE can be used as a corrosion-inhibiting layer for astronaut suits, according to the predicted results.

2022 ◽  
Vol 12 ◽  
Qian Liu ◽  
Jing Lin ◽  
Li Wen ◽  
Shaozhou Wang ◽  
Peng Zhou ◽  

The protein–protein association in cellular signaling networks (CSNs) often acts as weak, transient, and reversible domain–peptide interaction (DPI), in which a flexible peptide segment on the surface of one protein is recognized and bound by a rigid peptide-recognition domain from another. Reliable modeling and accurate prediction of DPI binding affinities would help to ascertain the diverse biological events involved in CSNs and benefit our understanding of various biological implications underlying DPIs. Traditionally, peptide quantitative structure-activity relationship (pQSAR) has been widely used to model and predict the biological activity of oligopeptides, which employs amino acid descriptors (AADs) to characterize peptide structures at sequence level and then statistically correlate the resulting descriptor vector with observed activity data via regression. However, the QSAR has not yet been widely applied to treat the direct binding behavior of large-scale peptide ligands to their protein receptors. In this work, we attempted to clarify whether the pQSAR methodology can work effectively for modeling and predicting DPI affinities in a high-throughput manner? Over twenty thousand short linear motif (SLiM)-containing peptide segments involved in SH3, PDZ and 14-3-3 domain-medicated CSNs were compiled to define a comprehensive sequence-based data set of DPI affinities, which were represented by the Boehringer light units (BLUs) derived from previous arbitrary light intensity assays following SPOT peptide synthesis. Four sophisticated MLMs (MLMs) were then utilized to perform pQSAR modeling on the set described with different AADs to systematically create a variety of linear and nonlinear predictors, and then verified by rigorous statistical test. It is revealed that the genome-wide DPI events can only be modeled qualitatively or semiquantitatively with traditional pQSAR strategy due to the intrinsic disorder of peptide conformation and the potential interplay between different peptide residues. In addition, the arbitrary BLUs used to characterize DPI affinity values were measured via an indirect approach, which may not very reliable and may involve strong noise, thus leading to a considerable bias in the modeling. The Rprd2 = 0.7 can be considered as the upper limit of external generalization ability of the pQSAR methodology working on large-scale DPI affinity data.

2022 ◽  
Vol 1 ◽  
Christopher R. Apostol ◽  
Kelsey Bernard ◽  
Parthasaradhireddy Tanguturi ◽  
Gabriella Molnar ◽  
Mitchell J. Bartlett ◽  

There is an unmet clinical need for curative therapies to treat neurodegenerative disorders. Most mainstay treatments currently on the market only alleviate specific symptoms and do not reverse disease progression. The Pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenous neuropeptide hormone, has been extensively studied as a potential regenerative therapeutic. PACAP is widely distributed in the central nervous system (CNS) and exerts its neuroprotective and neurotrophic effects via the related Class B GPCRs PAC1, VPAC1, and VPAC2, at which the hormone shows roughly equal activity. Vasoactive intestinal peptide (VIP) also activates these receptors, and this close analogue of PACAP has also shown to promote neuronal survival in various animal models of acute and progressive neurodegenerative diseases. However, PACAP’s poor pharmacokinetic profile (non-linear PK/PD), and more importantly its limited blood-brain barrier (BBB) permeability has hampered development of this peptide as a therapeutic. We have demonstrated that glycosylation of PACAP and related peptides promotes penetration of the BBB and improves PK properties while retaining efficacy and potency in the low nanomolar range at its target receptors. Furthermore, judicious structure-activity relationship (SAR) studies revealed key motifs that can be modulated to afford compounds with diverse selectivity profiles. Most importantly, we have demonstrated that select PACAP glycopeptide analogues (2LS80Mel and 2LS98Lac) exert potent neuroprotective effects and anti-inflammatory activity in animal models of traumatic brain injury and in a mild-toxin lesion model of Parkinson’s disease, highlighting glycosylation as a viable strategy for converting endogenous peptides into robust and efficacious drug candidates.

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 482
Li-Zhi Cheng ◽  
Dan-Ling Huang ◽  
Min Liao ◽  
Ke-Ming Li ◽  
Zhao-Qiu Wu ◽  

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 μM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure–activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

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