Three cheers for nitrogen: aza-DKPs, the aza analogues of 2,5-diketopiperazines

Maujean, Timothé; Girard, Nicolas; Ganesan, A.; Gulea, Mihaela; Bron, Dominique

doi:10.1039/d0ra09457a

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…Cyclo(His-Pro) is a cyclic dipeptide endogenous to the brain due to its structural similarity to tyreotropinreleasing hormone [269]. Its aza-analogs are a promising scaffold in the discovery of next-generation GABA inhibitors [270]. Piperazinediones reveal anxiolytic activity through the modulation of GABAergic transmission [271].…”

Section: Inhibitors Of Gabaergic Receptorsmentioning

confidence: 99%

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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Section: Inhibitors Of Gabaergic Receptorsmentioning

confidence: 99%

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

et al. 2021

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The IMS Library: from IN‐Stock to Virtual

Djikic‐Stojsic,

Bret,

Blond

et al. 2024

ChemMedChem

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A chemical library is a key element in the early stages of pharmaceutical research. Its design encompasses various factors, such as diversity, size, ease of synthesis, aimed at increasing the likelihood of success in drug discovery. This article explores the collaborative efforts of computational and synthetic chemists in tailoring chemical libraries for cost‐effective and resource‐efficient use, particularly in the context of academic research projects. It proposes chemoinformatics methodologies that address two pivotal questions: first, crafting a diverse panel of under 1000 compounds from an existing pool through synthetic efforts, leveraging the expertise of organic chemists; and second, expanding pharmacophoric diversity within this panel by creating a highly accessible virtual chemical library. Chemoinformatics tools were developed to analyse initial panel of about 10,000 compounds into two tailored libraries: eIMS and vIMS. The eIMS Library comprises 578 diverse in‐stock compounds ready for screening. Its virtual counterpart, vIMS, features novel compounds guided by chemists, ensuring synthetic accessibility. vIMS offers a broader array of binding motifs and improved drug‐like characteristics achieved through the addition of diverse functional groups to eIMS scaffolds followed by filtering of reactive or unusual structures. The uniqueness of vIMS is emphasized through a comparison with commercial suppliers' virtual chemical space.

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