Trends in peptide drug discovery

Muttenthaler, Markus; King, Glenn F.; Adams, David J.; Alewood, Paul F.

doi:10.1038/s41573-020-00135-8

Cited by 1,071 publications

(968 citation statements)

References 242 publications

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“…The critical issue is establishing the relationship of a specific PPI with a disease. Bioinformatics and a better understanding of human molecular physiology have a key role in decreasing time and cost in respect to experimental approaches for the identification of new targets ( Muttenthaler et al, 2021 ). Starting from the native sequence, that has been already identified by nature, the challenge of the medicinal chemist is then similar to the one of heterologous peptides, with the target to file a product patent that identifies a series of new structure in a very competitive environment.…”

Section: Current Challenges and Future Perspectives In Peptides Development As Therapeutic Agentsmentioning

confidence: 99%

Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives

Cabri

Cantelmi

Corbisiero

et al. 2021

Front. Mol. Biosci.

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Targeting protein-protein interactions (PPIs) has been recently recognized as an emerging therapeutic approach for several diseases. Up today, more than half a million PPI dysregulations have been found to be involved in pathological events. The dynamic nature of these processes and the involvement of large protein surfaces discouraged anyway the scientific community in considering them promising therapeutic targets. More recently peptide drugs received renewed attention since drug discovery has offered a broad range of structural diverse sequences, moving from traditionally endogenous peptides to sequences possessing improved pharmaceutical profiles. About 70 peptides are currently on the marked but several others are in clinical development. In this review we want to report the update on these novel APIs, focusing our attention on the molecules in clinical development, representing the direct consequence of the drug discovery process of the last 10 years. The comprehensive collection will be classified in function of the structural characteristics (native, analogous, heterologous) and on the basis of the therapeutic targets. The mechanism of interference on PPI will also be reported to offer useful information for novel peptide design.

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Section: Current Challenges and Future Perspectives In Peptides Development As Therapeutic Agentsmentioning

confidence: 99%

Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives

Cabri

Cantelmi

Corbisiero

et al. 2021

Front. Mol. Biosci.

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“…Peptide macrocycles constitute a signicant fraction of approved peptide therapeutics: around 30 out of 80 peptide drugs on the global market; macrocyclic topologies are prevalent among 150 peptides in clinical development and in 400-600 peptides undergoing preclinical studies. [1][2][3][4] Macrocyclization of peptides increases binding affinity, improves permeability through the cell membrane, and increases stability towards enzymatic hydrolysis compared to linear peptides. [5][6][7][8][9] The large surface area of macrocycles has been critical for identifying molecules that bind extended protein surfaces and inhibit protein-protein interactions.…”

Section: Introductionmentioning

confidence: 99%

Genetically-encoded discovery of proteolytically stable bicyclic inhibitors for morphogen NODAL

et al. 2021

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“…To overcome this limitation, some modifications are made to peptides in order to synthesize new molecules that biologically mimic peptides, such as peptidomimetics, for the development of useful therapeutic agents [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

1,2,3-Triazoles as Biomimetics in Peptide Science

2021

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Natural peptides are an important class of chemical mediators, essential for most vital processes. What limits the potential of the use of peptides as drugs is their low bioavailability and enzymatic degradation in vivo. To overcome this limitation, the development of new molecules mimicking peptides is of great importance for the development of new biologically active molecules. Therefore, replacing the amide bond in a peptide with a heterocyclic bioisostere, such as the 1,2,3-triazole ring, can be considered an effective solution for the synthesis of biologically relevant peptidomimetics. These 1,2,3-triazoles may have an interesting biological activity, because they behave as rigid link units, which can mimic the electronic properties of amide bonds and show bioisosteric effects. Additionally, triazole can be used as a linker moiety to link peptides to other functional groups.

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Trends in peptide drug discovery

Cited by 1,071 publications

References 242 publications

Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives

Therapeutic Peptides Targeting PPI in Clinical Development: Overview, Mechanism of Action and Perspectives

Genetically-encoded discovery of proteolytically stable bicyclic inhibitors for morphogen NODAL

1,2,3-Triazoles as Biomimetics in Peptide Science

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