Linking sequence patterns and functionality of alpha-helical antimicrobial peptides

2018 ◽  
Vol 35 (16) ◽  
pp. 2713-2717 ◽  
Author(s):  
Igor E Eliseev ◽  
Ivan N Terterov ◽  
Anna N Yudenko ◽  
Olga V Shamova
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design ◽  
Therapeutic Potential ◽  
Deep Understanding ◽  
Supplementary Information ◽  
Helical Conformation ◽  
Efficient Design ◽  
Sequence Patterns ◽  
Functional Features ◽  
Natural Peptides

Abstract Motivation The rational design of antimicrobial peptides (AMPs) with increased therapeutic potential requires deep understanding of the determinants of their activities. Inspired by the computational linguistic approach, we hypothesized that sequence patterns may encode the functional features of AMPs. Results We found that α-helical and β-sheet peptides have non-intersecting pattern sets and therefore constructed new sequence templates using only helical patterns. Designed peptides adopted an α-helical conformation upon binding to lipids, confirming that the method captures structural and biophysical properties. In the antimicrobial assay, 5 of 7 designed peptides exhibited activity against Gram(+) and Gram(–) bacteria, with most potent candidate comparable to best natural peptides. We thus conclude that sequence patterns comprise the structural and functional features of α-helical AMPs and guide their efficient design. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals G4Killer web application: a tool to design G-quadruplex mutations

2020 ◽  
Vol 36 (10) ◽  
pp. 3246-3247
Author(s):  
Vaclav Brazda ◽  
Jan Kolomaznik ◽  
Jean-Louis Mergny ◽  
Jiri Stastny
Keyword(s):  
Dna Sequences ◽  
Web Application ◽  
Rational Design ◽  
Therapeutic Potential ◽  
Supplementary Information ◽  
Web Tool ◽  
Web Based ◽  
Dna Structures ◽  
G Quadruplex ◽  
User Friendly

Abstract Motivation G-quadruplexes (G4) are important regulatory non-B DNA structures with therapeutic potential. A tool for rational design of mutations leading to decreased propensity for G4 formation should be useful in studying G4 functions. Although tools exist for G4 prediction, no easily accessible tool for the rational design of G4 mutations has been available. Results We developed a web-based tool termed G4Killer that is based on the G4Hunter algorithm. This new tool is a platform-independent and user-friendly application to design mutations crippling G4 propensity in a parsimonious way (i.e., keeping the primary sequence as close as possible to the original one). The tool is integrated into our DNA analyzer server and allows for generating mutated DNA sequences having the desired lowered G4Hunter score with minimal mutation steps. Availability and implementation The G4Killer web tool can be accessed at: http://bioinformatics.ibp.cz. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals USING SEQUENCE PATTERNS TO IDENTIFY AND DESIGN NEW ANTIMICROBIAL PEPTIDES

2019 ◽  
Vol 19 (1S) ◽  
pp. 162-164
Author(s):  
I E Eliseev ◽  
I N Terterov ◽  
O V Shamova
Keyword(s):  
Antimicrobial Peptides ◽  
Synthetic Peptides ◽  
Comprehensive Analysis ◽  
Characteristic Sequence ◽  
Natural Antimicrobial ◽  
Sequence Patterns ◽  
Sheet Structure ◽  
Functional Features ◽  
Computational Identification ◽  
Β Sheet

Natural antimicrobial peptides (AMPs) are remarkably diverse, yet they all share some common structural and functional features. In an attempt to find what determines similar activities of non-homologous molecules, we performed a comprehensive analysis of sequence patterns in AMPs. We found that natural AMPs possess characteristic sequence patterns, and these patterns differ for peptides with α-helical and β-sheet structure. We showed that the patterns facilitate computational identification of AMPs in databases. We then used patterns to design new peptides, synthesized them and assayed for antibacterial activity. The most active among synthetic peptides exhibited activity against Gram(+) and Gram(-) pathogens comparable to best natural AMPs.

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

Solution structures of stomoxyn and spinigerin, two insect antimicrobial peptides with an α-helical conformation

Biopolymers ◽  
2006 ◽  
Vol 81 (2) ◽  
pp. 92-103 ◽  
Author(s):  
Céline Landon ◽  
Hervé Meudal ◽  
Nathalie Boulanger ◽  
Philippe Bulet ◽  
Françoise Vovelle
Keyword(s):  
Antimicrobial Peptides ◽  
Helical Conformation ◽  
Solution Structures

A Review of Antimicrobial Peptides: Its Function, Mode of Action and Therapeutic Potential

2022 ◽  
Vol 28 (1) ◽  
Author(s):  
Sehrish Nayab ◽  
Muhammad Aamir Aslam ◽  
Sajjad ur Rahman ◽  
Zia ud Din Sindhu ◽  
Sanaullah Sajid ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Mode Of Action ◽  
Therapeutic Potential

scholarly journals Rational Design of Cyclic Antimicrobial Peptides Based on BPC194 and BPC198

Molecules ◽  
2017 ◽  
Vol 22 (7) ◽  
pp. 1054 ◽  
Author(s):  
Anna Cirac ◽  
Maria Torné ◽  
Esther Badosa ◽  
Emilio Montesinos ◽  
Pedro Salvador ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Rational Design

scholarly journals CancerGram: An Effective Classifier for Differentiating Anticancer from Antimicrobial Peptides

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1045
Author(s):  
Michał Burdukiewicz ◽  
Katarzyna Sidorczuk ◽  
Dominik Rafacz ◽  
Filip Pietluch ◽  
Mateusz Bąkała ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Cancer Cells ◽  
Plasma Membranes ◽  
Therapeutic Potential ◽  
Kappa Statistic ◽  
R Package ◽  
Bioactive Molecules ◽  
Membrane Composition ◽  
Anticancer Peptides ◽  
Multicellular Organisms

Antimicrobial peptides (AMPs) constitute a diverse group of bioactive molecules that provide multicellular organisms with protection against microorganisms, and microorganisms with weaponry for competition. Some AMPs can target cancer cells; thus, they are called anticancer peptides (ACPs). Due to their small size, positive charge, hydrophobicity and amphipathicity, AMPs and ACPs interact with negatively charged components of biological membranes. AMPs preferentially permeabilize microbial membranes, but ACPs additionally target mitochondrial and plasma membranes of cancer cells. The preference towards mitochondrial membranes is explained by their membrane potential, membrane composition resulting from α-proteobacterial origin and the fact that mitochondrial targeting signals could have evolved from AMPs. Taking into account the therapeutic potential of ACPs and millions of deaths due to cancer annually, it is of vital importance to find new cationic peptides that selectively destroy cancer cells. Therefore, to reduce the costs of experimental research, we have created a robust computational tool, CancerGram, that uses n-grams and random forests for predicting ACPs. Compared to other ACP classifiers, CancerGram is the first three-class model that effectively classifies peptides into: ACPs, AMPs and non-ACPs/non-AMPs, with AU1U amounting to 0.89 and a Kappa statistic of 0.65. CancerGram is available as a web server and R package on GitHub.

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