Rational Design of Cholesterol Derivative for Improved Stability of Paclitaxel Cationic Liposomes

2018 ◽  
Vol 35 (4) ◽  
Author(s):  
Jasmin Monpara ◽  
Chryso Kanthou ◽  
Gillian M. Tozer ◽  
Pradeep R. Vavia
Keyword(s):  
Rational Design ◽  
Cationic Liposomes ◽  
Improved Stability ◽  
Cholesterol Derivative

scholarly journals Rational design of MgF2 catalysts with long-term stability for the dehydrofluorination of 1,1-difluoroethane (HFC-152a)

RSC Advances ◽  
2019 ◽  
Vol 9 (41) ◽  
pp. 23744-23751 ◽  
Author(s):  
Haodong Tang ◽  
Mingming Dang ◽  
Yuzhen Li ◽  
Lichun Li ◽  
Wenfeng Han ◽  
...  
Keyword(s):  
Rational Design ◽  
Sol Gel ◽  
Hard Template ◽  
Term Stability ◽  
Long Term Stability ◽  
Improved Stability ◽  
Hfc 152A ◽  
Template Methods

In this study, sol–gel, precipitation and hard-template methods were applied to synthesize MgF2 catalysts with improved stability towards dehydrofluorination of hydrofluorocarbons and MgF2-T catalysts demonstrated superior long-term stability.

scholarly journals Peptides with Dual Antimicrobial–Anticancer Activity: Strategies to Overcome Peptide Limitations and Rational Design of Anticancer Peptides

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4245
Author(s):  
Yamil Liscano ◽  
Jose Oñate-Garzón ◽  
Jean Paul Delgado
Keyword(s):  
Anticancer Activity ◽  
In Silico ◽  
Rational Design ◽  
A Priori ◽  
Current Status ◽  
Anticancer Properties ◽  
Anticancer Peptides ◽  
In Silico Studies ◽  
Wide Range ◽  
Improved Stability

Peptides are naturally produced by all organisms and exhibit a wide range of physiological, immunomodulatory, and wound healing functions. Furthermore, they can provide with protection against microorganisms and tumor cells. Their multifaceted performance, high selectivity, and reduced toxicity have positioned them as effective therapeutic agents, representing a positive economic impact for pharmaceutical companies. Currently, efforts have been made to invest in the development of new peptides with antimicrobial and anticancer properties, but the poor stability of these molecules in physiological environments has triggered a bottleneck. Therefore, some tools, such as nanotechnology and in silico approaches can be applied as alternatives to try to overcome these obstacles. In silico studies provide a priori knowledge that can lead to the development of new anticancer peptides with enhanced biological activity and improved stability. This review focuses on the current status of research in peptides with dual antimicrobial–anticancer activity, including advances in computational biology using in silico analyses as a powerful tool for the study and rational design of these types of peptides.

scholarly journals Proof of concept for rational design of hepatitis C virus E2 core nanoparticle vaccines

2020 ◽  
Vol 6 (16) ◽  
pp. eaaz6225 ◽  
Author(s):  
Linling He ◽  
Netanel Tzarum ◽  
Xiaohe Lin ◽  
Benjamin Shapero ◽  
Cindy Sou ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
B Cell ◽  
Neutralizing Antibodies ◽  
Rational Design ◽  
Vaccine Development ◽  
Variable Region ◽  
Improved Stability ◽  
Cell Patterns ◽  
Neutralizing Epitopes

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are responsible for cell entry, with E2 being the major target of neutralizing antibodies (NAbs). Here, we present a comprehensive strategy for B cell–based HCV vaccine development through E2 optimization and nanoparticle display. We redesigned variable region 2 in a truncated form (tVR2) on E2 cores derived from genotypes 1a and 6a, resulting in improved stability and antigenicity. Crystal structures of three optimized E2 cores with human cross-genotype NAbs (AR3s) revealed how the modified tVR2 stabilizes E2 without altering key neutralizing epitopes. We then displayed these E2 cores on 24- and 60-meric nanoparticles and achieved substantial yield and purity, as well as enhanced antigenicity. In mice, these nanoparticles elicited more effective NAb responses than soluble E2 cores. Next-generation sequencing (NGS) defined distinct B cell patterns associated with nanoparticle-induced antibody responses, which target the conserved neutralizing epitopes on E2 and cross-neutralize HCV genotypes.

scholarly journals Novel approaches for the rational design of PROTAC linkers

2020 ◽  
Vol 1 (5) ◽  
pp. 381-390
Author(s):  
Almaz Zagidullin ◽  
Vasili Milyukov ◽  
Albert Rizvanov ◽  
Emil Bulatov
Keyword(s):  
Ubiquitin Ligase ◽  
Computer Aided Design ◽  
Rational Design ◽  
E3 Ubiquitin Ligase ◽  
Cell Membrane Permeability ◽  
Structural Components ◽  
Attachment Sites ◽  
Recent Developments ◽  
Improved Stability ◽  
Aided Design

Proteolysis targeting chimeras (PROTACs) represent a promising class of hetero-bivalent molecules that facilitate ubiquitination of a target protein by simultaneously binding and bringing together both the E3 enzyme and the target. These compounds consist of three structural components: two ligands one of which binds the protein of interest (POI) while the other binds an E3 ubiquitin ligase to promote POI ubiquitination, and a linker connecting both moieties. Recent developments in the field highlight the fact that linker composition and length play a crucial role in achieving optimal PROTAC properties, modulate binding kinetics and substantially impacts the potency and selectivity. In this review, the authors briefly discuss the recent findings in PROTAC design approaches with focus on the linker. For each PROTAC such linker parameters as chemical nature, length, hydrophilicity and rigidity have to be optimized to achieve improved stability, bioavailability cell membrane permeability and suitable spatial orientation between the target POI and the E3 ubiquitin ligase. Thus rational linker design with respect to composition, length and attachment sites is essential for the development of potent PROTAC compounds. Computer-aided design and novel innovative linker strategies, such as PROTAC shortening, photo-switchable PROTACs, in-cell click-formed CLIPTACs, “click chemistry” approaches are also discussed in the review.

scholarly journals Rhodaelectro-catalyzed access to chromones via formyl C–H activation towards peptide electro-labeling

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maximilian Stangier ◽  
Antonis M. Messinis ◽  
João C. A. Oliveira ◽  
Hao Yu ◽  
Lutz Ackermann
Keyword(s):  
Natural Products ◽  
Pharmaceutical Industry ◽  
Binding Affinity ◽  
Enzymatic Degradation ◽  
Rational Design ◽  
Cell Permeability ◽  
Structural Motif ◽  
Improved Stability ◽  
Considerable Impact ◽  
Privileged Scaffold

AbstractChromones represent a privileged scaffold in medicinal chemistry and are an omnipresent structural motif in natural products. Chemically encoded non-natural peptidomimetics feature improved stability towards enzymatic degradation, cell permeability and binding affinity, translating into a considerable impact on pharmaceutical industry. Herein, a strategy for the sustainable assembly of chromones via electro-formyl C–H activation is presented. The rational design of the rhodaelectro-catalysis is guided by detailed mechanistic insights and provides versatile access to tyrosine-based fluorogenic peptidomimetics.

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