A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies
Abstract
As a versatile therapeutic modality, peptides attract much attention because of their great binding affinity, low toxicity, and the capability of targeting traditionally “undruggable” protein surfaces. However, the deficiency of cell permeability and metabolic stability always limits the success of in vitro bioactive peptides as drug candidates. Peptide macrocyclization is one of the most established strategies to overcome these limitations. Over the past decades, more than 40 cyclic peptide drugs have been clinically approved, the vast majority of which are derived from natural products. The de novo discovered cyclic peptides on the basis of rational design and in vitro evolution, have also enabled the binding with targets for which nature provides no solutions. The current review summarizes different classes of cyclic peptides with diverse biological activities, and presents an overview of various approaches to develop cyclic peptide-based drug candidates, drawing upon series of examples to illustrate each strategy.
Jing X, Jin K. A gold mine for drug discovery: Strategies to develop cyclic peptides into therapies. Med Res Rev. 2019 Oct 9. doi: 10.1002/med.21639. Review. PubMed PMID: 31599007.
The Botanical Garden of Department of Pharmacognosy, University of Vienna, Austria. Photo by Atanas G. Atanasov.
Lagoon of the seven cities, a twin lake in the crater of a dormant volcano in the western part of the São Miguel island (Azores, Portugal). Photo by Dr. Ana Sanches Silva.
Central Australian desert scene. Photo by Dr. Rohan Davis.
HEK293T cells. Photo by Atanas G. Atanasov.
Tropical rainforest, Queensland, Australia. Photo by Dr. Rohan Davis.
Australian ocean scene. Photo by Dr. Rohan Davis.
Laboratory equipment. Photo by Atanas G. Atanasov.
Rhododendron arboreum flower. Photo by Devesh Tewari.
The Valley of Flowers, Himalaya, India. Photo by Dr. Rajeshwari Singh.
Bryce Canyon, Utah, USA. Photo by Dr. Anupam Bishayee.
Euphorbia prolifera Buch. (Ham) Ex. Photo by Devesh Tewari.
Foothills of Himalaya, India. Photo by Devesh Tewari.
The Valley of Flowers, Himalaya, India. Photo by Dr. Rajeshwari Singh.
Eco-School Festival, Leiria-Portugal, Spring 2018
Polygonum maritimum (L.) (Polygonaceae)- Ourdania beach (Ain Temouchent- west Algeria)- taken by PhD. EL HACI Imad Abdelhamid
Flower blossoms at gardens by the bay Singapore-photo by Dr. Hemanth Kumar Boyina.
