Carbohydrates in Peptide and Protein Design

Jensen, Knud J.; Brask, Jesper

doi:10.1002/9780470749708.ch5

Cited by 6 publications

(7 citation statements)

References 87 publications

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“…Protein de novo design offers a test of our understanding of the factors controlling protein structure, folding and stability. The approach also offers the prospect of access to tailor-made proteins 9 10 11 12 13 14 15 16 17 . One way to overcome the complexity of protein folding is the concept of template-assembled synthetic proteins (TASPs) 18 19 .…”

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confidence: 99%

Peptide–oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

et al. 2016

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Peptide-based structures can be designed to yield artificial proteins with specific folding patterns and functions. Template-based assembly of peptide units is one design option, but the use of two orthogonal self-assembly principles, oligonucleotide triple helix and a coiled coil protein domain formation have never been realized for de novo protein design. Here, we show the applicability of peptide–oligonucleotide conjugates for self-assembly of higher-ordered protein-like structures. The resulting nano-assemblies were characterized by ultraviolet-melting, gel electrophoresis, circular dichroism (CD) spectroscopy, small-angle X-ray scattering and transmission electron microscopy. These studies revealed the formation of the desired triple helix and coiled coil domains at low concentrations, while a dimer of trimers was dominating at high concentration. CD spectroscopy showed an extraordinarily high degree of α-helicity for the peptide moieties in the assemblies. The results validate the use of orthogonal self-assembly principles as a paradigm for de novo protein design.

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Peptide–oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

et al. 2016

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“…Inspired by natural detoxification systems, and based on our recent accomplishments with cyclic tetrapeptides [17] and GSH‐analogs, [18] we envisioned that two units of GSH cyclized together would provide the necessary macrocyclic cavity and enough binding moieties to strongly capture Pb(II) ions. The cyclic design was chosen to improve metabolic stability [19] and for imposing conformational constraints on the peptide to achieve a more defined three‐dimensional structure [20] …”

Section: Introductionmentioning

confidence: 99%

Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification

et al. 2022

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A rationally‐designed scaffold of cyclic octapeptides composed of two units of the natural tripeptide glutathione (GSH) was optimized to strongly and selectively capture toxic lead ions (Pb(II)). Using state‐of‐the‐art computational tools, a list of eleven plausible peptides was shortened to five analogs based on their calculated affinity to Pb(II) ions. We then synthesized and investigated them for their abilities to recover Pb‐poisoned human cells. A clear pattern was observed from the in vitro detoxification results, indicating the importance of cavity size and polar moieties to enhance metal capturing. These, together with the apparent benefit of cyclizing the peptides, improved the detoxification of the two lead peptides by approximately two folds compared to GSH and the benchmark chelating agents against Pb poisoning. Moreover, the two peptides did not show any toxicity and, therefore, were thoroughly investigated to determine their potential as next‐generation remedies for Pb poisoning.

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“…They are frequently antimicrobial and toxic in nature. These properties have various medical applications as antibiotics, immunosuppressive agents 42 . Generally, the thin layer chromatography technique is used for the detection of cyclic peptides in crude extracts of biomass 43 .…”

Section: Introductionmentioning

confidence: 99%

Opportunistic Challenges of Computer-aided Drug Discovery of Lipopeptides: New Insights for Large Molecule Therapeutics

Yadav¹,

Eswari²

2022

AJMB

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Computer-aided drug designing is a promising approach to defeating the dry pipeline of drug discovery. It aims at reduced experimental efforts with cost-effectiveness. Naturally occurring large molecules with molecular weight higher than 500 Dalton such as cationic peptides, cyclic peptides, glycopeptides and lipopeptides are a few examples of large molecules which have successful applications as the broad spectrum antibacterial, anticancer, antiviral, antifungal and antithrombotic drugs. Utilization of microbial metabolites as potential drug candidates incur cost effectiveness through large scale production of such molecules rather than a synthetic approach. Computational studies on such compounds generate tremendous possibilities to develop novel leads with challenges to handle these complex molecules with available computational tools. The opportunities begin with the desired structural modifications in the parent drug molecule. Virtual modifications followed by molecular interaction studies at the target site through molecular modeling simulations and identification of structure-activity relationship models to develop more prominent and potential drug molecules. Lead optimization studies to develop novel compounds with increased specificity and reduced off targeting is a big challenge computationally for large molecules. Prediction of optimized pharmacokinetic properties facilitates development of a compound with lower toxicity as compared to the natural compounds. Generating the library of compounds and studies for target specificity and ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) for large molecules are laborious and incur huge cost and chemical wastage through in-vitro methods. Hence, computational methods need to be explored to develop novel compounds from natural large molecules with higher specificity. This review article is focusing on possible challenges and opportunities in the pathway of computer-aided drug discovery of large molecule therapeutics.

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Carbohydrates in Peptide and Protein Design

Cited by 6 publications

References 87 publications

Peptide–oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

Peptide–oligonucleotide conjugates as nanoscale building blocks for assembly of an artificial three-helix protein mimic

Cyclic Octapeptides Composed of Two Glutathione Units Outperform the Monomer in Lead Detoxification

Opportunistic Challenges of Computer-aided Drug Discovery of Lipopeptides: New Insights for Large Molecule Therapeutics

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