scholarly journals Impact of Dehydroamino Acids on the Structure and Stability of Incipient 310-Helical Peptides

2019 ◽  
Vol 85 (3) ◽  
pp. 1601-1613 ◽  
Author(s):  
Daniel Joaquin ◽  
Michael A. Lee ◽  
David W. Kastner ◽  
Jatinder Singh ◽  
Shardon T. Morrill ◽  
...  
Keyword(s):  
Helical Peptides ◽  
Dehydroamino Acids ◽  
Structure And Stability

scholarly journals Impact of Dehydroamino Acids on the Structure and Stability of Incipient 3₁₀ Helical Peptides

2019 ◽  
Author(s):  
Daniel Joaquin ◽  
Michael A. Lee ◽  
David W. Kastner ◽  
Jatinder Singh ◽  
Shardon T. Morrill ◽  
...  
Keyword(s):  
Room Temperature ◽  
Bioactive Peptides ◽  
Elevated Temperatures ◽  
Peptide Structure ◽  
Helical Peptides ◽  
Dehydroamino Acids ◽  
Structure And Stability ◽  
Helical Peptide ◽  
Proteolytic Stability ◽  
The Impact

<div>A comparative study of the impact of small, medium-sized, and bulky Δ,Δ-dehydroamino acids (ΔAAs) on the structure and stability of Balaram’s incipient 3₁₀ -helical peptide (1) is reported. Replacement of the N-terminal Aib residue of 1 with a ΔAA afforded peptides 2a–c that maintained the 310-helical shape of 1 in solution. In contrast, installation of a ΔAA in place of Aib-3 yielded peptides 3a–c that preferred a Δ-sheet-like conformation. The impact of the ΔAA on peptide structure was independent of size, with small (ΔAla), medium-sized (Z-ΔAbu), and bulky (ΔVal) ΔAAs exerting similar effects. The proteolytic stabilities of 1 and its analogs were determined by incubation with Pronase. Z-ΔAbu and ΔVal increased the resistance of peptides to proteolysis when incorporated at the 3-position and had negligible impact on stability when placed at the 1-position, whereas ΔAla-containing peptides degraded rapidly regardless of position. Exposure of peptides 2a–c and 3a–c to the reactive thiol cysteamine revealed that ΔAla-containing peptides underwent conjugate addition at room temperature, while Z-ΔAbu- and ΔVal-containing peptides were inert even at elevated temperatures. These results suggest that both bulky and the more synthetically accessible medium-sized ΔAAs should be valuable tools for bestowing rigidity and proteolytic stability on bioactive peptides.</div>

scholarly journals Impact of Dehydroamino Acids on the Structure and Stability of Incipient 3₁₀ Helical Peptides

2019 ◽  
Author(s):  
Daniel Joaquin ◽  
Michael A. Lee ◽  
David W. Kastner ◽  
Jatinder Singh ◽  
Shardon T. Morrill ◽  
...  
Keyword(s):  
Room Temperature ◽  
Bioactive Peptides ◽  
Elevated Temperatures ◽  
Peptide Structure ◽  
Helical Peptides ◽  
Dehydroamino Acids ◽  
Structure And Stability ◽  
Helical Peptide ◽  
Proteolytic Stability ◽  
The Impact

<div>A comparative study of the impact of small, medium-sized, and bulky Δ,Δ-dehydroamino acids (ΔAAs) on the structure and stability of Balaram’s incipient 3₁₀ -helical peptide (1) is reported. Replacement of the N-terminal Aib residue of 1 with a ΔAA afforded peptides 2a–c that maintained the 310-helical shape of 1 in solution. In contrast, installation of a ΔAA in place of Aib-3 yielded peptides 3a–c that preferred a Δ-sheet-like conformation. The impact of the ΔAA on peptide structure was independent of size, with small (ΔAla), medium-sized (Z-ΔAbu), and bulky (ΔVal) ΔAAs exerting similar effects. The proteolytic stabilities of 1 and its analogs were determined by incubation with Pronase. Z-ΔAbu and ΔVal increased the resistance of peptides to proteolysis when incorporated at the 3-position and had negligible impact on stability when placed at the 1-position, whereas ΔAla-containing peptides degraded rapidly regardless of position. Exposure of peptides 2a–c and 3a–c to the reactive thiol cysteamine revealed that ΔAla-containing peptides underwent conjugate addition at room temperature, while Z-ΔAbu- and ΔVal-containing peptides were inert even at elevated temperatures. These results suggest that both bulky and the more synthetically accessible medium-sized ΔAAs should be valuable tools for bestowing rigidity and proteolytic stability on bioactive peptides.</div>

scholarly journals Impact of oxetane incorporation on the structure and stability of alpha-helical peptides

2020 ◽  
Vol 22 (43) ◽  
pp. 25075-25083
Author(s):  
Eleanor S. Jayawant ◽  
Jonathan D. Beadle ◽  
Ina Wilkening ◽  
Piotr Raubo ◽  
Michael Shipman ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Helical Peptides ◽  
Structure And Stability ◽  
Alpha Helical Peptides

Here we reveal the tolerance of oxetane modification within alpha helical peptides using a combined molecular dynamics and experimental biophysics approach.

Polyplex: A Promising Gene Delivery System

2019 ◽  
Vol 12 (6) ◽  
pp. 4681-4686
Author(s):  
Rohan Aggarwal ◽  
Monika Targhotra ◽  
Bhumika Kumar ◽  
P.K Sahoo ◽  
Meenakshi K Chauhan
Keyword(s):  
Gene Transfer ◽  
Gene Delivery ◽  
Delivery System ◽  
Viral Vectors ◽  
Gene Delivery System ◽  
Cationic Polymers ◽  
Therapeutic Application ◽  
Promising Alternative ◽  
Structure And Stability ◽  
The Past

In the past few years gene delivery system has gained a huge attention owing to its proved efficacy in several diseases especially in those caused by genetic and/oroncological malfunctioning. The effective gene delivery mainly depends on the carrier molecules that can ensure the safe and specific delivery of the nucleic acidmolecules. Viral vectors have been used for a longer period as the gene transfer vehicle. However, these viral vectors have potential immunological disadvantages that made them less preferred. Recently, non-viral vectors such as polyplexes have emerged as a promising alternative for viral vectors. Polyplexes are formed by conjugating a polymer with DNA and in maximum cases the cationic polymers are preferred over others. The structure and stability of the polyplexes depends on various factors. The ability of the polymer to condense the DNA mainly dictates the efficiency of the polyplex mediated transfection. In this review we are going to provide a framework for the synthesis and design of the polyplexes along with the structure and stability of the complexes pertaining to mechanism of action, characterization and therapeutic application, including polyethyleneimine mediated cytotoxicity as well as newer strategies for the generation of better polyplexes.

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