Browsing by Subject "peptide synthesis"

Now showing 1 - 2 of 2

De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities
(PLOS One, 2013-11-26) Murugan, Ravichandran N.; Jacob, Binu; Ahn, Mija; Hwang, Eunha; Sohn, Hoik; Park, Hyo-Nam; Lee, Eunjung; Seo, Ji-Hyung; Cheong, Chaejoon; Nam, Ky-Youb; Hyun, Jae-Kyung; Jeong, Ki-Woong; Kim, Yangmee; Shin, Song Yub; Bang, Jeong Kyu
Background: Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability.-- Methodology/Principal Findings: In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. -- Conclusion/Significance: The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.
TORC Bonding Pairs as an Alternative to Nucleobases in Self Replicating Polymers
(2020-11) van der Stok, Aevi; Anslyn, Eric V.
The search for life on other planets is limited due to having only an incomplete knowledge of the origins of life on Earth as reference. While genetic information is stored and replicated by RNA and DNA using nucleobase chemistry here on Earth, this may not be the case on other planets with different environmental conditions. Tunable Orthogonal Reversible Covalent (TORC) bonds have promise in the creation of sequence-specific replicators because their orthogonality allows for the TORC bonding pairs to function similarly to nucleotide bases, defining and replicating the sequence, while their reversibility allows for duplexes to be separated for replication and their increased strength as covalent bonds would make these replicators more suitable to hot environments than the hydrogen bonding interactions observed in DNA replicators. This project represents the first step in the creation of sequence-specific TORC replicators by demonstrating the templating and synthesis of short peptide strands from a template strand using the hydrazone TORC bonding pair. In addition to this, macrocyclic products were also produced using these templates. This unexpected result holds promise for the creation of macrocyclic TORC replicators. The creation of macrocycles also has therapeutic applications, as macrocyclic peptides have useful properties but are generally difficult to synthesize, and the templates created in this project can quantitatively produce macrocyclic peptide products without any unwanted side products.