The Current State of Peptide Drug Discovery: Back to the Future?

Henninot, Antoine; Collins, James C.; Nuss, John M.

doi:10.1021/acs.jmedchem.7b00318

Cited by 848 publications

(779 citation statements)

References 295 publications

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“…Peptide‐based therapeutic agents offer enormous potential for addressing unmet medical needs due to their high specificity, efficacy, and safety 1. In the last decade, considerable efforts have been devoted to find bioactive peptides possessing wound healing properties for developing effective wound care treatments.…”

Section: Introductionmentioning

confidence: 99%

Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

et al. 2018

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In the past few years, there have been many efforts underway to develop effective wound healing treatments for traumatic injuries. In particular, wound‐healing peptides (WHPs) and peptide‐grafted dressings hold great promise for novel therapeutic strategies for wound management. This study reports a topical formulation of a new synthetic WHP (REGRT, REG) embedded in a hyaluronic acid (HA)‐based hydrogel dressing for the enhancement of acute excisional wound repair. The copper‐free click chemistry is utilized to form biocompatible HA hydrogels by cross‐linking dibenzocyclooctyl‐functionalized HA with 4‐arm poly(ethylene glycol) (PEG) azide. The HA hydrogels are grafted with the REG peptide, a functional derivative of erythroid differentiation regulator1, displaying potent cell motility‐stimulating ability, thus sustainably releasing physiologically active peptides for a prolonged period. Combined with the traditional wound healing benefits of HA, the HA hydrogel embedded REG (REG‐HAgel) accelerates re‐epithelialization in skin wound healing, particularly by promoting migration of fibroblasts, keratinocytes, and endothelial cells. REG‐HAgels improve not only rate, but quality of wound healing with higher collagen deposition and more microvascular formation while being nontoxic. The peptide‐grafted HA hydrogel system can be considered as a promising new wound dressing formulation strategy for the treatment of different types of wounds with combinations of various natural and synthetic WHPs.

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Section: Introductionmentioning

confidence: 99%

Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

et al. 2018

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“…( 2) The large surface-tovolumer atio of am icro-flow reactor enables rapid heat transfer for precise reactiont emperature control. ( 2) The large surface-tovolumer atio of am icro-flow reactor enables rapid heat transfer for precise reactiont emperature control.…”

Section: Introductionmentioning

confidence: 99%

Peptide Synthesis Utilizing Micro‐flow Technology

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Nakamura

2018

Chemistry An Asian Journal

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Peptide drugs have garnered much attention in recent years. However, conventional peptides ynthesis requires an excessa mount of expensive reagents of low atom economy,a nd the large amount of waste produced by these reagents complicates the purification of desired peptides. Solid-phase approaches simplify the purification of these peptides, but these requiree xpensive solid-phase, excess amounts of reagents,s ubstrates, and solvents. This makes it important to develop high-yielding, cost-effective, andl ess wasteful synthetic approaches. Micro-flow technology (reac-tion space 1mm) has produced manya dvantages over conventional batch synthesis. Thea dvantages include precise control of short reactiont ime and temperature, high levels of light penetration efficiency,l oweredr isks of handling dangerous compounds, and ready scale-up withh igh reproducibility.M icro-flow peptides yntheses using these advantages have been reported in recent years. This review summarizes the solid-phase and solution-phases yntheses of a-a nd b-peptides and of cyclic peptidesu sing micro-flow technology.[a] Dr.

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“…[1] Peptides are often glycosylated to improve the solubility, biological stability,a nd lower the immunogenicity.T he oligosaccharides of natural glycoproteins play ak ey role in molecular recognition, [2][3][4] and asparagine (Asn) residues are one of the major sites for glycosylation in glycoproteins. [1] Peptides are often glycosylated to improve the solubility, biological stability,a nd lower the immunogenicity.T he oligosaccharides of natural glycoproteins play ak ey role in molecular recognition, [2][3][4] and asparagine (Asn) residues are one of the major sites for glycosylation in glycoproteins.…”

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confidence: 99%

Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis

2019

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The direct 2-deoxyglycosylation of nucleophiles with glycals leads to biologically and pharmacologically important 2-deoxysugar compounds.A lthough the direct addition of hydroxyl and sulfonamide groups have been well developed, the direct 2-deoxyglycosylation of amide groups has not been reported to date.H erein, we show the first direct 2-deoxyglycosylation of amide groups using an ewly designed Brønsted acid catalyst under mild conditions.T hrough mechanistic investigations,w ed iscovered that the amide group can inhibit acid catalysts,a nd the inhibition has made the 2-deoxyglycosylation reaction difficult. Diffusion-ordered two-dimensional NMR spectroscopya nalysis implied that the 2-chloroazolium salt catalyst was less likely to form aggregates with amides in comparison to other acid catalysts.The chlorine atom and the extended p-scaffold of the catalyst played acrucial role for this phenomenon. This relative insusceptibility to inhibition by amides is more responsible for the catalytic activity than the strength of the acidity.Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

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The Current State of Peptide Drug Discovery: Back to the Future?

Cited by 848 publications

References 295 publications

Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

Development of Biocompatible HA Hydrogels Embedded with a New Synthetic Peptide Promoting Cellular Migration for Advanced Wound Care Management

Peptide Synthesis Utilizing Micro‐flow Technology

Direct Addition of Amides to Glycals Enabled by Solvation‐Insusceptible 2‐Haloazolium Salt Catalysis

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