Characterization of novel human intragenic antimicrobial peptides, incorporation and release studies from ureasil-polyether hybrid matrix

Mariano, Giuseppina; Sa, Lyakhov; Silva, E.M. Carmo da; Santos, M.A.; Fh, José L. Cardozo; Lira, Bianca O.V.; Barbosa, Éder Alves; Araújo, Alyne Rodrigues de; Leite, J. R.; Ramada, Marcelo Henrique Soller; Bloch, Carlos; Oliveira, Aline; Chaker, Juliano Alexandre; Brand, Guilherme D.

doi:10.1016/j.msec.2020.111581

Cited by 10 publications

(7 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported by several studies that the same helical peptide resolved by NMR (at high concentration) has a higher helicity percentage than that of the same measured by CD (at a lower concentration). For instance, an intragenic AMP (PDB ID: 6VLA) has a helicity percentage of 94% according to its NMR-resolved structure but 59% by CD 48 . Similarly, an AMP from Whiteleg shrimp (PDB ID: 2N1C) has 65 and 35% helicity percentage when structurally resolved by NMR and CD, respectively 49 .…”

Section: Discussionmentioning

confidence: 99%

Helical structure motifs made searchable for functional peptide design

Tsai

Salawu

et al. 2022

Nat Commun

View full text Add to dashboard Cite

The systematic design of functional peptides has technological and therapeutic applications. However, there is a need for pattern-based search engines that help locate desired functional motifs in primary sequences regardless of their evolutionary conservation. Existing databases such as The Protein Secondary Structure database (PSS) no longer serves the community, while the Dictionary of Protein Secondary Structure (DSSP) annotates the secondary structures when tertiary structures of proteins are provided. Here, we extract 1.7 million helices from the PDB and compile them into a database (Therapeutic Peptide Design database; TP-DB) that allows queries of compounded patterns to facilitate the identification of sequence motifs of helical structures. We show how TP-DB helps us identify a known purification-tag-specific antibody that can be repurposed into a diagnostic kit for Helicobacter pylori. We also show how the database can be used to design a new antimicrobial peptide that shows better Candida albicans clearance and lower hemolysis than its template homologs. Finally, we demonstrate how TP-DB can suggest point mutations in helical peptide blockers to prevent a targeted tumorigenic protein-protein interaction. TP-DB is made available at http://dyn.life.nthu.edu.tw/design/.

show abstract

Section: Discussionmentioning

confidence: 99%

Helical structure motifs made searchable for functional peptide design

Tsai

Salawu

et al. 2022

Nat Commun

View full text Add to dashboard Cite

show abstract

“…The peptides used in this work were BatxC (KRFKKFFKKLKNSVKKRVKKFFRKPRVIGVTFPF-NH 2 ; molecular mass = 4257.41 kDa), BatxC(C-2.14Phe)des-Phe1 (KRFKKFFKKLKNSVKKRVKFFFRKPRVIGVTFP-NH 2 ; molecular mass = 4128.65 kDa), and BatxC(C-2.15Phe) (KRFKKFFKKLKNSVKKRVKFFFRKPRVIGVTFPF-NH 2 ; molecular mass = 4275.76 kDa), all synthesized by SPPS using Fmoc/tBu chemistry and a rink amide resin (Sigma, 0.7 mmol/g) as solid support . The products of the synthesis were then purified by HPLC with a reverse phase C18 column (250 × 20 mm i.d., 15 μm, Shim-Pack PREP-ODS).…”

Section: Methodsmentioning

confidence: 99%

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

et al. 2021

View full text Add to dashboard Cite

Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, BatxC(C-2.15Phe) and BatxC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.

show abstract

“…A different strategy is the search for so-called intragenic or encrypted peptides, which are internal sequences of proteins that present biological activity (Lemes et al, 2016;Mariano et al, 2021). The prospection of those molecules could consist of an in silico alignment of conserved sequences of encrypted peptides against the peptides of interest (Brand et al, 2019;Mariano et al, 2021) or by enzymatic hydrolyses of a secretion, tissue, or a crude protein extract of an organism followed by activity assays and fractionation (Lemes et al, 2016;Lee and Hur, 2017). The latter technique was used to identify two antiproliferative peptides from tuna dark muscle after its hydrolyses with papain and protease XXIII.…”

Section: Prospecting Bioactive Peptides From Marine Organismsmentioning

confidence: 99%

Marine Organisms as a Rich Source of Biologically Active Peptides

et al. 2021

View full text Add to dashboard Cite

Oceanic environments are one of the largest sources of bioactive molecules, due to the high degree of biodiversity and the innumerable ecological relationships established between macro and microorganisms found in the different ecosystems of these complex environments. Marine organisms are being studied increasingly because they are considered important producers of biologically active peptides. Peptides extracted from marine sources have different functions and structures, when compared to peptides isolated from terrestrial sources, considering the different adaptive pressures undergone by these organisms throughout the evolutionary process. Most bioactive compounds isolated from marine environments are obtained from symbiont microorganisms. Of these microorganisms, bacteria are an important source of bioactive peptides, isolated by metagenomic studies from complex gene networks expressed under marine conditions. Several peptides have been shown to have biotechnological properties such as antimicrobial, antitumor, antihypertensive, anticoagulant, anti-fouling, and antioxidant activity and can be used in the pharmaceutical and food industries. This review article aims to provide an overview of peptides of biotechnological importance, isolated from different phyla of marine organisms, examining the relationship between structure and function of some of these peptides, as well as the ways of extracting, purifying and prospecting new peptides by traditional methods of isolation or sequence analysis in databases. It also intends to list the peptides that are already being produced and used by the industry, in its various branches, and their current state in the market and in clinical tests.

show abstract

Characterization of novel human intragenic antimicrobial peptides, incorporation and release studies from ureasil-polyether hybrid matrix

Cited by 10 publications

References 39 publications

Helical structure motifs made searchable for functional peptide design

Helical structure motifs made searchable for functional peptide design

Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)

Marine Organisms as a Rich Source of Biologically Active Peptides

Contact Info

Product

Resources

About