Disulfide engineering on temporin‐SHf: Stabilizing the bioactive conformation of an ultra‐short antimicrobial peptide

In Silico searching for short antimicrobial peptides has revealed temporin‐SHf as the short (8AA), hydrophobic, broad spectrum, and natural antimicrobial peptide. Important drawback associated with temporin‐SHf is the susceptibility of its bioactive conformation for denaturation and proteolytic degradation. In the current report, disulfide engineering strategy has been adopted to improve the stability of bioactive conformation of temporin‐SHf. The functionally non‐critical Leu4 and Ile7 residues at i and i + 3 position of helical conformation of temporin‐SHf were mutated with cysteine disulfide. Designed [L4C, I7C]temporin‐SHf was synthesized, characterized using NMR spectroscopy, and accessed for antimicrobial activity. [L4C, I7C]Temporin‐SHf adopts helical conformation from Phe3 to Phe8 in the absence of membrane‐mimetic environment and retains broad spectrum antimicrobial activity. The reduction potential of cysteine disulfide of [L4C, I7C]temporin‐SHf is −289 mV. Trypsin‐induced digestion and serum‐induced digestion have confirmed the advantage of cysteine disulfide in imparting proteolytic stability to temporin‐SHf. Disulfide‐stabilized temporin‐SHf may serve as a good model for the rational design of temporin‐SHf based antibiotics for treatment of infectious diseases.

• Publication year

  2019

• Venue

  Chemical Biology and Drug Design

• Publication date

  2019-09-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1111/cbdd.13525PMID 30924306
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• 2017 FDA Peptide Harvest

  2018cited by this paper
• Design and surface immobilization of short anti-biofilm peptides.

  2017cited by this paper
• Structural space of intramolecular peptide disulfides: Analysis of peptide toxins retrieved from venomous peptide databases

  2017cited by this paper
• The therapeutic applications of antimicrobial peptides (AMPs): a patent review

  2017cited by this paper
• Short AntiMicrobial Peptides (SAMPs) as a class of extraordinary promising therapeutic agents

  2016cited by this paper
• Antimicrobial Peptides: An Emerging Category of Therapeutic Agents

  2016cited by this paper
• Discovery, structure, function, and applications of cyclotides: circular proteins from plants.

  2016cited by this paper
• CAMPR3: a database on sequences, structures and signatures of antimicrobial peptides

  2015cited by this paper
• Naturally Occurring Peptides from Rana temporaria: Antimicrobial Properties and More.

  2015cited by this paper
• APD3: the antimicrobial peptide database as a tool for research and education

  2015cited by this paper
• Structure-Activity Relationship-based Optimization of Small Temporin-SHf Analogs with Potent Antibacterial Activity.

  2015influential reference
• Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity

  2014cited by this paper
• Synthetic analogs of anoplin show improved antimicrobial activities

  2013cited by this paper
• Complex cocktails: the evolutionary novelty of venoms.

  2013cited by this paper
• Physiology of invertebrate oxytocin and vasopressin neuropeptides

  2013cited by this paper
• Antimicrobial peptides stage a comeback

  2013cited by this paper
• Dissecting a role of evolutionary‐conserved but noncritical disulfide bridges in cysteine‐rich peptides using ω‐conotoxin GVIA and its selenocysteine analogs

  2012cited by this paper
• Tuning the activity of a short arg-trp antimicrobial Peptide by lipidation of a C- or N-terminal lysine side-chain.

  2012cited by this paper
• Cysteine-rich mini-proteins in human biology.

  2012cited by this paper
• Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics

  2012cited by this paper
• Discovery, biosynthesis, and engineering of lantipeptides.

  2012cited by this paper
• YADAMP: yet another database of antimicrobial peptides.

  2012cited by this paper
• In Vitro Activities of LTX-109, a Synthetic Antimicrobial Peptide, against Methicillin-Resistant, Vancomycin-Intermediate, Vancomycin-Resistant, Daptomycin-Nonsusceptible, and Linezolid-Nonsusceptible Staphylococcus aureus

  2012cited by this paper
• Extremely abundant antimicrobial peptides existed in the skins of nine kinds of Chinese odorous frogs.

  2012cited by this paper
• Evolution of three-finger toxins - a versatile mini protein scaffold.

  2011cited by this paper
• The expanding scope of antimicrobial peptide structures and their modes of action.

  2011cited by this paper
• Designing antimicrobial peptides: form follows function

  2011cited by this paper
• Evolution of three-finger toxins - a versatile mini protein scaffold.

  2011cited by this paper
• NMR Structure Implications of Enhanced Efficacy of Obestatin Fragment Analogs

  2011cited by this paper
• Temporin-SHf, a New Type of Phe-rich and Hydrophobic Ultrashort Antimicrobial Peptide*

  2010influential reference
• 310 helices in channels and other membrane proteins

  2010cited by this paper
• Cyclic peptides as potential therapeutic agents for skin disorders

  2010cited by this paper
• Discovery and applications of the plant cyclotides.

  2010cited by this paper
• Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

  2010cited by this paper
• Disulfide conformation and design at helix N‐termini

  2009cited by this paper
• Chapter 3:Redox Potentials of Cysteine Residues in Peptides and Proteins: Methods for their Determination

  2008influential reference
• Folding of Conotoxins: Formation of the Native Disulfide Bridges During Chemical Synthesis and Biosynthesis of Conus Peptides

  2008cited by this paper
• Selenoglutathione: efficient oxidative protein folding by a diselenide.

  2007cited by this paper
• Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies

  2006cited by this paper
• α-Selenoconotoxins, a New Class of Potent α7 Neuronal Nicotinic Receptor Antagonists*

  2006cited by this paper
• Limited tendency of α‐helical residues to form disulfide bridges: a structural explanation

  2006cited by this paper
• Structure and stability of the alpha-helix: lessons for design.

  2006cited by this paper
• Alpha-selenoconotoxins, a new class of potent alpha7 neuronal nicotinic receptor antagonists.

  2006cited by this paper
• Limited tendency of alpha-helical residues to form disulfide bridges: a structural explanation.

  2006cited by this paper
• Temporins, anti-infective peptides with expanding properties

  2006influential reference
• High-throughput generation of small antibacterial peptides with improved activity

  2005cited by this paper
• Bulky nonproteinogenic amino acids permit the design of very small and effective cationic antibacterial peptides.

  2004cited by this paper
• Conus venoms: a rich source of novel ion channel-targeted peptides.

  2004cited by this paper
• Structure-Function Relationship Studies on the Frog Skin Antimicrobial Peptide Tigerinin 1: Design of Analogs with Improved Activity and Their Action on Clinical Bacterial Isolates

  2002cited by this paper
• Redox-active cyclic bis(cysteinyl)peptides as catalysts for in vitro oxidative protein folding.

  2002cited by this paper
• Design of folded peptides.

  2001cited by this paper
• A linear endothelin-1 analogue: solution structure of ET-1[Aib1,3,11,15, Nle7] by nuclear magnetic resonance spectroscopy and molecular modelling.

  1999cited by this paper
• Introduction to the NMR of proteins.

  1997cited by this paper
• Scorpion toxins as natural scaffolds for protein engineering.

  1995cited by this paper
• Thiol/disulfide exchange equilibria and disulfide bond stability.

  1995cited by this paper
• Kinetics and Equilibria of the Formation and Reduction of the Disulfide Bonds in Arginine-Vasopressin and Oxytocin by Thiol/Disulfide Interchange with Glutathione and Cysteine

  1994cited by this paper
• Redox potentials of active-site bis(cysteinyl) fragments of thiol-protein oxidoreductases.

  1993cited by this paper
• Structure-function studies of amphiphilic antibacterial peptides.

  1993cited by this paper
• Appendix 5. Nomenclature for peptide fragment ions (positive ions).

  1990cited by this paper
• Thermodynamics of Stacking and of Self‐Association of the Dinucleoside Monophosphate m62A‐U from Proton NMR Chemical Shifts:

  1982cited by this paper
• Thermodynamics of stacking and of self-association of the dinucleoside monophosphate m2(6)A-U from proton NMR chemical shifts: differential concentration temperature profile method.

  1982cited by this paper

• Antimicrobial and antitumor properties of anuran peptide temporin-SHf induce apoptosis in A549 lung cancer cells

  2024cites this paper
• Strategies employed in the design of antimicrobial peptides with enhanced proteolytic stability.

  2022cites this paper
• Design and modification of frog skin peptide brevinin-1GHa with enhanced antimicrobial activity on Gram-positive bacterial strains

  2022cites this paper
• Significance of D- tryptophan in Contryphan-Ar1131 Conus peptide: Oxidative folding, trypsin binding, and photostabilization activity.

  2022cites this paper
• The Redox-Active Conopeptide Derived from the Venom Duct Transcriptome of Conus lividus Assists in the Oxidative Folding of Conotoxin.

  2021cites this paper
• Antimicrobial Peptides and Peptidomimetics for the Control of Antimicrobial Resistance

  2021cites this paper
• Antimicrobial Effect of a Peptide Containing Novel Oral Spray on Streptococcus mutans

  2020cites this paper