Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

Scarel, Marco; Marchesan, Silvia

doi:10.3390/molecules26113376

Cited by 31 publications

(29 citation statements)

References 120 publications

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“…Considering that the shorter the motif, the lower and easier will be the cost of production, it is thus not surprising that ultra-short peptides are amongst the most attractive supramolecular peptide gelators [46]. In particular, cyclic [47][48][49] or linear dipeptides [50][51][52][53][54][55] are amongst the simplest options as building blocks for hydrogels, however, tripeptides are better positioned for bioactivity. Indeed, it was shown that 25 atoms other than hydrogen constitute the ideal size for drugs and drug-like molecules for maximal ligand-binding efficacy and bioactivity, and this number corresponds to the average number for a tripeptide [56].…”

Section: Self-assembling Short Peptides With Bioactive Motifs For Hyd...mentioning

confidence: 99%

Self-Assembled Peptide Nanostructures for ECM Biomimicry

Marin

Marchesan

2022

Nanomaterials

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Proteins are functional building blocks of living organisms that exert a wide variety of functions, but their synthesis and industrial production can be cumbersome and expensive. By contrast, short peptides are very convenient to prepare at a low cost on a large scale, and their self-assembly into nanostructures and gels is a popular avenue for protein biomimicry. In this Review, we will analyze the last 5-year progress on the incorporation of bioactive motifs into self-assembling peptides to mimic functional proteins of the extracellular matrix (ECM) and guide cell fate inside hydrogel scaffolds.

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Section: Self-assembling Short Peptides With Bioactive Motifs For Hyd...mentioning

confidence: 99%

Self-Assembled Peptide Nanostructures for ECM Biomimicry

Marin

Marchesan

2022

Nanomaterials

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“…In this context, they have high stability, while the costs of production are low. Moreover, they can be produced and modified in large quantities in an easy way [370]. DKP-based low molecular weight gelators also find applications in encapsulation of drugs [74,370].…”

Section: Supramolecular Structuring Of Dkpsmentioning

confidence: 99%

“…Moreover, they can be produced and modified in large quantities in an easy way [370]. DKP-based low molecular weight gelators also find applications in encapsulation of drugs [74,370]. Self-assembled functional proline containing DKP-based bio-nano-materials have superior structural rigidity and in vivo stability provided by the DKP ring.…”

Section: Supramolecular Structuring Of Dkpsmentioning

confidence: 99%

“…They can cross the blood-brain barrier, and reach difficult pathological targets, offering versatility of desirable biophysical properties. They have broad-spectrum prospectives in bio-medicine, such as high strength biomaterials, isothermal, and injectable gelation in (stimuli-responsive) the delivery of drugs and other bioactive molecules (as well as gene), or 3D bio-printing, smart bio-nano-architectonics, microfluidic devices, bio-sensing, and point-of-care diagnostics, hierarchical biomimetics [367,370]. DKP nanostructures can encapsulate biomolecules, fluorescent dyes and deliver them inside cells.…”

Section: Supramolecular Structuring Of Dkpsmentioning

confidence: 99%

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Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

et al. 2021

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Cyclic dipeptides, also know as diketopiperazines (DKP), the simplest cyclic forms of peptides widespread in nature, are unsurpassed in their structural and bio-functional diversity. DKPs, especially those containing proline, due to their unique features such as, inter alia, extra-rigid conformation, high resistance to enzyme degradation, increased cell permeability, and expandable ability to bind a diverse of targets with better affinity, have emerged in the last years as biologically pre-validated platforms for the drug discovery. Recent advances have revealed their enormous potential in the development of next-generation theranostics, smart delivery systems, and biomaterials. Here, we present an updated review on the biological and structural profile of these appealing biomolecules, with a particular emphasis on those with anticancer properties, since cancers are the main cause of death all over the world. Additionally, we provide a consideration on supramolecular structuring and synthons, based on the proline-based DKP privileged scaffold, for inspiration in the design of compound libraries in search of ideal ligands, innovative self-assembled nanomaterials, and bio-functional architectures.

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“…21 The synthetic molecules, metabolites, or natural products with CDP core showed numerous biological activities such as anticancer, antimalarial, antimicrobials, hypoglycaemic agents, quorum sensing, blood-brain barrier (BBB) transporters, drug delivery vehicles, tissue engineering, and so on. [22][23][24][25][26][27][28] CDPs exhibit high structural rigidity, low enzymatic degradation, high physiological stability, and exceptional biological activity as compared to their linear counterparts. 19,29 Limited conformational mobility and presence of four hydrogen-bonding sites (two donors and two acceptors) of two cis amide groups in CDPs 30,31 strongly encourage the self-assembly and formation of gels.…”

Section: Introductionmentioning

confidence: 99%

S‐Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release

Ghosh

Nag

Saha

et al. 2022

Journal of Peptide Science

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Peptide-based low molecular weight supramolecular hydrogels hold promising aspects in various fields of application especially in biomaterial and biomedical sciences such as drug delivery, wound healing, tissue engineering, cell proliferation, and so on due to their extreme biocompatibility. Unlike linear peptides, cyclic peptides have more structural rigidity and tolerance to enzymatic degradation and high environmental stability which make them even better candidates for the above-said applications. Herein, a new small cyclic dipeptide (CDP) cyclo-(Leu-S-Bzl-Cys) (P1) consisting of L-leucine and S-benzyl protected L-cysteine was reported which formed a hydrogel at physiological conditions (at 37 C and pH = 7.46). The hydrogel formed from the cyclic dipeptide P1 showed very good tolerance towards environmental parameters such as pH and temperature and was seen to be stable for more than a year without any deformation. The hydrogel was thermoreversible and stable in the pH range 6-12. Mechanical strength of P1 hydrogel was measured by rheology experiments. Atomic force microscopy (AFM) and field emission scanning electron microscopy (FE-SEM) images revealed that, in aqueous solvents, P1 self-assembled into a highly cross-linked nanofibrillar network which immobilized water molecules inside the cages and formed the hydrogel. The self-assembled cyclic dipeptide acquired the antiparallel β-sheet secondary structure, which was evident from CD and Fourier transform infrared (FT-IR) studies. The β-sheet arrangement and formation of amyloid fibrils were further established by ThT binding assay. Furthermore, P1 was able to form a hydrogel in the presence of the anticancer drug 5-fluorouracil (5FU), and sustainable release of the drug from the hydrogel was measured in vitro.The hydrogelator P1 showed almost no cytotoxicity towards the human colorectal cancer cell line HCT116 up to a considerably high concentration and showed potential application in sustainable drug delivery. The co-assembly of 5FU and P1 hydrogel exhibited much better anticancer activity towards the HCT116 cancer cell line than 5FU alone and decreased the IC 50 dose of 5FU to a much lower value.

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Diketopiperazine Gels: New Horizons from the Self-Assembly of Cyclic Dipeptides

Cited by 31 publications

References 120 publications

Self-Assembled Peptide Nanostructures for ECM Biomimicry

Self-Assembled Peptide Nanostructures for ECM Biomimicry

Cyclic Dipeptides: The Biological and Structural Landscape with Special Focus on the Anti-Cancer Proline-Based Scaffold

S‐Benzyl cysteine based cyclic dipeptide super hydrogelator: Enhancing efficacy of an anticancer drug via sustainable release

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